Structural and mechanistic basis of the EMC-dependent biogenesis of distinct transmembrane clients
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Abstract
Membrane protein biogenesis in the endoplasmic reticulum (ER) is complex and failure-prone. The ER membrane protein complex (EMC), comprising eight conserved subunits, has emerged as a central player in this process. Yet, we have limited understanding of how EMC enables insertion and integrity of diverse clients, from tail-anchored to polytopic transmembrane proteins. Here, yeast and human EMC cryo-EM structures reveal conserved intricate assemblies and human-specific features associated with pathologies. Structure-based functional studies distinguish between two separable EMC activities, as an insertase regulating tail-anchored protein levels and a broader role in polytopic membrane protein biogenesis. These depend on mechanistically coupled yet spatially distinct regions including two lipid-accessible membrane cavities which confer client-specific regulation, and a non-insertase EMC function mediated by the EMC lumenal domain. Our studies illuminate the structural and mechanistic basis of EMC’s multifunctionality and point to its role in differentially regulating the biogenesis of distinct client protein classes.
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Cites
UCSF Chimera—A visualization system for exploratory research and analysis
Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., & Ferrin, T. E. (2004) · Journal of Computational Chemistry · doi:10.1002/jcc.20084 · Cited by 45,260 · cited 1× · see citing works
“Molecular graphics and analyses were performed with the UCSF Chimera package (Pettersen et al., 2004) and Coot 0.”
Method<i>Coot</i> : model-building tools for molecular graphics
Emsley, P., & Cowtan, K. (2004) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444904019158 · Cited by 30,571 · see citing works
Touw, W. G., & Vriend, G. (n.d.) · doi:10.1107/s09074449 · Cited by 18,392
Cox, J., & Mann, M. (2008) · Nature Biotechnology · doi:10.1038/nbt.1511 · Cited by 14,855 · see citing works
Krogh, A., Larsson, B., von Heijne, G., & Sonnhammer, E. L. L. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2000.4315 · Cited by 12,654 · see citing works
The Phyre2 web portal for protein modeling, prediction and analysis
Kelley, L. A., Mezulis, S., Yates, C. M., Wass, M. N., & Sternberg, M. J. E. (2015) · Nature Protocols · doi:10.1038/nprot.2015.053 · Cited by 9,652 · cited 5× · see citing works
“Fab DH4 starting structure was computed using Phyre2 1-to-1 threading against a crystal structure of a monoclonal Fab (PDB 1M71, Vyas, 2002).”
MethodInfluentialMotionCor2 - anisotropic correction of beam-induced motion for improved cryo-electron microscopy
Zheng, S., Palovcak, E. J., Armache, J., Verba, K., Cheng, Y.-F., & Agard, D. (2017) · Nature Methods · doi:10.1038/nmeth.4193 · Cited by 7,678 · see citing works
T-Coffee: A novel method for fast and accurate multiple sequence alignment.
Notredame, C., Higgins, D., & Heringa, J. (2000) · Journal of Molecular Biology · doi:10.1006/jmbi.2000.4042 · Cited by 7,321 · see citing works
Liebschner, D. C., Afonine, P. V., Baker, M. L., Bunkòczi, G., Chen, V. B., Croll, T. I., Hintze, B. J., Hung, L., Jain, S., McCoy, A. J., et al. (2019) · Acta Crystallographica Section D Structural Biology · doi:10.1107/s2059798319011471 · Cited by 6,709 · see citing works
Global quantification of mammalian gene expression control
Schwanhäusser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., Chen, W., & Selbach, M. (2011) · Nature · doi:10.1038/nature10098 · Cited by 6,566 · see citing works
I-TASSER: a unified platform for automated protein structure and function prediction
Roy, A., Küçükural, A., & Zhang, Y. (2010) · Nature Protocols · doi:10.1038/nprot.2010.5 · Cited by 6,093 · see citing works
Protein secondary structure prediction based on position-specific scoring matrices.
Jones, D. C. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1999.3091 · Cited by 5,741 · cited 1× · see citing works
“…Quick2D, a tool within the Max-Plank Institute for Developmental Biology Bioinformatics Toolkit that visualizes several different secondary structure predictors (Jones, 1999; Cuff and Barton, 1999; Ouali and King, 2000; Rost, 2001; Lupas, 1991; Jones, 1994; Ward, 2004; Peng, 2006; Obradovic, 2005).”
MethodThe I-TASSER Suite: protein structure and function prediction
Yang, J., Yan, R., Roy, A., Xu, D., Poisson, J., & Zhang, Y. (2015) · Nature Methods · doi:10.1038/nmeth.3213 · Cited by 5,596 · cited 2× · see citing works
“, 2013), I-TASSER (Zhang, 2008; Roy et al., 2010; Yang et al., 2015), Phyre2 (Kelley et al.”
Automated electron microscope tomography using robust prediction of specimen movements.
Mastronarde, D. (2005) · Journal of Structural Biology · doi:10.1016/j.jsb.2005.07.007 · Cited by 5,446 · see citing works
UCSF ChimeraX: Meeting modern challenges in visualization and analysis
Goddard, T. D., Huang, C. C., Meng, E. C., Pettersen, E. F., Couch, G. S., Morris, J. H., & Ferrin, T. E. (2018) · Protein Science · doi:10.1002/pro.3235 · Cited by 5,267 · cited 4× · see citing works
“All of the visualization and structure figures were made using UCSF ChimeraX 1.0 (Goddard, 2018) and UCSF Chimera 1.14 (Pettersen, 2004).”
BackgroundInfluentialWickersham, I. R., Sullivan, H., & Seung, H. (2010) · Nature Protocols · doi:10.1038/nprot.2009.248 · Cited by 4,905 · cited 2× · see citing works
“, 2013), I-TASSER (Zhang, 2008; Roy et al., 2010; Yang et al., 2015), Phyre2 (Kelley et al.”
Rappsilber, J., Mann, M., & Ishihama, Y. (2007) · Nature Protocols · doi:10.1038/nprot.2007.261 · Cited by 4,641 · see citing works
New tools for automated high-resolution cryo-EM structure determination in RELION-3
Zivanov, J., Nakane, T., Forsberg, B., Kimanius, D., Hagen, W., Lindahl, E., & Scheres, S. (2018) · eLife · doi:10.7554/elife.42166 · Cited by 4,377 · see citing works
Predicting coiled coils from protein sequences.
Lupas, A., Van Dyke, M., & Stock, J. (1991) · Science · doi:10.1126/science.252.5009.1162 · Cited by 3,953 · cited 2× · see citing works
“, 2015) and Quick2D, a tool within the Max-Plank Institute for Developmental Biology Bioinformatics Toolkit that visualizes several different secondary structure predictors (Jones, 1999; Cuff and Barton, 2000; Ouali and King, 2000; Rost, 2001; Lupas et al., 1991; Jones et al., 1994; Ward et al., 2004; Peng et al., 200…”
MethodDiscriminative topological features reveal biological network mechanisms
Middendorf, M., Ziv, E., Adams, C., Hom, J., Koytcheff, R., Levovitz, C., Woods, G., Chen, L., & Wiggins, C. (2004) · BMC Bioinformatics · doi:10.1186/1471-2105-5-181 · Cited by 3,913 · cited 1× · see citing works
“Next several homology models were computed and overlain for yEMC2, with a predicted TPR structural domain, using Robetta (Raman, 2009; Song, 2013), I-TASSER (Zhang, 2008; Roy, 2010; Yang, 2015), Phyre2 (Kelley, 2015), and RaptorX (Kallberg, 2012).”
MethodGctf: Real-time CTF determination and correctionPreprint
Zhang, K. (2015) · bioRxiv · doi:10.1101/022376 · Cited by 3,644 · cited 6× · see citing works
“Cryo-EM data processing for hEMC in detergent Preprocessing in Focus included dose-weighted motion correction using Motioncor2 (Zheng, 2017), CTF estimation using Gctf (Zhang, 2016) and templated autopicking using Gautomatch (Kai Zhang).”
BackgroundMethodInfluentialReal-space refinement in PHENIX for cryo-EM and crystallography
Afonine, P., Poon, B., Read, R. J., Sobolev, O., Terwilliger, T., Urzhumtsev, A., & Adams, P. (2018) · bioRxiv · doi:10.1107/s2059798318006551 · Cited by 3,057 · see citing works
Genome-Scale CRISPR-Mediated Control of Gene Repression and Activation
Gilbert, L. A., Horlbeck, M. A., Adamson, B., Villalta, J. E., Chen, Y., Whitehead, E. H., Guimaraes, C., Panning, B., Ploegh, H. L., Bassik, M. C., et al. (2014) · Cell · doi:10.1016/j.cell.2014.09.029 · Cited by 2,728 · see citing works
Self-citationA Completely Reimplemented MPI Bioinformatics Toolkit with a New HHpred Server at its Core
Zimmermann, L., Stephens, A., Nam, S.-Z., Rau, D., Kübler, J., Lozajic, M., Gabler, F., Söding, J., Lupas, A. N., & Alva, V. (2018) · Journal of Molecular Biology · doi:10.1016/j.jmb.2017.12.007 · Cited by 2,522 · cited 1× · see citing works
“Inspection of structural homology and secondary structure predictions for the hEMC subunits produced via HHpred and Quick2D servers (Zimmermann, 2018) predicted the luminal domain of EMC1, the largest hEMC subunit, to consist of two beta-propellers.”
BackgroundPrediction and Functional Analysis of Native Disorder in Proteins from the Three Kingdoms of Life
Ward, J. J., Sodhi, J. S., McGuffin, L. J., Buxton, B. F., & Jones, D. T. (2004) · Journal of Molecular Biology · doi:10.1016/j.jmb.2004.02.002 · Cited by 2,010 · cited 1× · see citing works
“, 2015) and Quick2D, a tool within the Max-Plank Institute for Developmental Biology Bioinformatics Toolkit that visualizes several different secondary structure predictors (Jones, 1999; Cuff and Barton, 2000; Ouali and King, 2000; Rost, 2001; Lupas et al., 1991; Jones et al., 1994; Ward et al., 2004; Peng et al., 200…”
MethodLi, X.-M., Mooney, P., Zheng, S., Booth, C., Braunfeld, M. B., Gubbens, S., Agard, D., & Cheng, Y.-F. (2013) · Nature Methods · doi:10.1038/nmeth.2472 · Cited by 1,866 · see citing works
Non-uniform refinement: adaptive regularization improves single-particle cryo-EM reconstructionPreprint
Punjani, A., Zhang, H.-W., & Fleet, D. J. (2019) · Nature Methods · doi:10.1101/2019.12.15.877092 · Cited by 1,580 · cited 2× · see citing works
“of non-uniform refinement in cryoSPARC (Punjani et al., 2017; Punjani et al., 2019) further improved the map quality and overall resolution to 3.”
BackgroundMethodTemplate-based protein structure modeling using the RaptorX web server
Källberg, M., Wang, H., Wang, S., Peng, J., Wang, Z., Lu, H. J., & Xu, J. (2012) · Nature Protocols · doi:10.1038/nprot.2012.085 · Cited by 1,576 · see citing works
Targeting, disruption, replacement, and allele rescue: integrative DNA transformation in yeast.
Rothstein, R. (1991) · Methods in Enzymology · doi:10.1016/0076-6879(91)94022-5 · Cited by 1,283 · see citing works
High-throughput discovery of novel developmental phenotypes
The International Mouse Phenotyping Consortium, Dickinson, M. E., Flenniken, A. M., Ji, X., Teboul, L., Wong, M. D., White, J. K., Meehan, T. F., Weninger, W. J., Westerberg, H., et al. (2016) · Nature · doi:10.1038/nature19356 · Cited by 1,196 · see citing works
Structure of TPR Domain–Peptide Complexes
Scheufler, C., Brinker, A., Bourenkov, G., Pegoraro, S., Moroder, L., Bartunik, H., Hartl, F. U., & Moarefi, I. (2000) · Cell · doi:10.1016/s0092-8674(00)80830-2 · Cited by 1,188 · see citing works
Collaboration gets the most out of software
Morin, A., Eisenbraun, B., Key, J., Sanschagrin, P. C., Timony, M. A., Ottaviano, M., & Piotr Sliz, A. (2013) · eLife · doi:10.7554/elife.01456 · Cited by 1,095 · cited 2× · see citing works
“Model building and refinement of yEMC in nanodiscs Structural biology applications used in this project were compiled and configured by SBGrid (Morin, 2013).”
MethodHigh-Resolution Comparative Modeling with RosettaCM
Song, Y., DiMaio, F., Wang, R. Y., Kim, D. E., Miles, C., Brunette, T., Thompson, J., & Baker, D. A. (2013) · Structure · doi:10.1016/j.str.2013.08.005 · Cited by 1,079 · cited 1× · see citing works
“Next several homology models were computed and overlain for yEMC2, with a predicted TPR structural domain, using Robetta (Raman, 2009; Song, 2013), I-TASSER (Zhang, 2008; Roy, 2010; Yang, 2015), Phyre2 (Kelley, 2015), and RaptorX (Kallberg, 2012).”
MethodAccelerated cryo-EM structure determination with parallelisation using GPUs in RELION-2
Kimanius, D., Forsberg, B., Scheres, S., & Lindahl, E. (2016) · bioRxiv · doi:10.1101/059717 · Cited by 990
OMIM.org: leveraging knowledge across phenotype–gene relationships
Amberger, J., Bocchini, C. A., Scott, A., & Hamosh, A. (2018) · Nucleic Acids Res. · doi:10.1093/nar/gky1151 · Cited by 977 · see citing works
Length-dependent prediction of protein intrinsic disorder
Peng, K., Predrag Radivojac, A., Vučetić, S., Dunker, A. K., & Zoran Obradovic, A. (2006) · BMC Bioinformatics · doi:10.1186/1471-2105-7-208 · Cited by 926 · see citing works
The Phenix Software for Automated Determination of Macromolecular Structures
Adams, P., Afonine, P., Bunkoczi, G., Chen, V. B., Echols, N., Headd, J., Hung, L., Jain, S., Kapral, G. J., Grosse-Kunstleve, R., et al. (2011) · Methods · doi:10.1016/j.ymeth.2011.07.005 · Cited by 912 · cited 11× · see citing works
“, 2010) and refined using Phenix real-space refinement (Adams et al., 2011).”
BackgroundMethodInfluentialReconstitution of Membrane Proteins in Phospholipid Bilayer Nanodiscs
Ritchie, T. K., Grinkova, Y., Bayburt, T. H., Denisov, I., Zolnerciks, J. K., Atkins, W. M., & Sligar, S. (2009) · Methods in Enzymology · doi:10.1016/s0076-6879(09)64011-8 · Cited by 827 · see citing works
Jones, D. T., Taylor, W. R., & Thornton, J. M. (1994) · Biochemistry · doi:10.1021/bi00176a037 · Cited by 779 · see citing works
Cuff, J. A., & Barton, G. J. (2000) · Proteins Structure Function and Bioinformatics · doi:10.1002/1097-0134(20000815)40:3 · Cited by 768 · see citing works
Screening and large-scale expression of membrane proteins in mammalian cells for structural studies
Goehring, A., Lee, C.-H., Wang, K. H., Michel, J. C., Claxton, D. P., Baconguis, I., Althoff, T., Fischer, S., Garcia, K., & Gouaux, E. (2014) · Nature Protocols · doi:10.1038/nprot.2014.173 · Cited by 716 · cited 3× · see citing works
“For hEMC, all subunits were overexpressed together with Flag-tagged EMC5 via a single recombinant BacMam virus.”
MethodInfluentialVolmer, R., van der Ploeg, K., & Ron, D. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1217611110 · Cited by 655 · see citing works
Exploiting heterogeneous sequence properties improves prediction of protein disorder
Zoran Obradovic, A., Peng, K., Vučetić, S., Predrag Radivojac, A., & Dunker, A. K. (2005) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.20735 · Cited by 554 · see citing works
YidC mediates membrane protein insertion in bacteria.
Samuelson, J. C., Chen, M., Jiang, F., Möller, I., Wiedmann, M., Kuhn, A., Phillips, G. J., & Dalbey, R. E. (2000) · Nature · doi:10.1038/35020586 · Cited by 538 · see citing works
Review: Protein Secondary Structure Prediction Continues to Rise
Rost, B. (2001) · Journal of Structural Biology · doi:10.1006/jsbi.2001.4336 · Cited by 534 · cited 1× · see citing works
“…Quick2D, a tool within the Max-Plank Institute for Developmental Biology Bioinformatics Toolkit that visualizes several different secondary structure predictors (Jones, 1999; Cuff and Barton, 1999; Ouali and King, 2000; Rost, 2001; Lupas, 1991; Jones, 1994; Ward, 2004; Peng, 2006; Obradovic, 2005).”
MethodStructure prediction for CASP8 with all‐atom refinement using Rosetta
Raman, S., Vernon, R. M., Thompson, J., Tyka, M. D., Sadreyev, R. I., Pei, J., Kim, D. E., Kellogg, E. H., DiMaio, F., Lange, O. F., et al. (2009) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.22540 · Cited by 511 · see citing works
Shaikh, T., Gao, H., Baxter, W., Asturias, F., Boisset, N., Leith, A., & Frank, J. (2008) · Nature Protocols · doi:10.1038/nprot.2008.156 · Cited by 499 · see citing works
Defining human ERAD networks through an integrative mapping strategy
Christianson, J. C., Olzmann, J. A., Shaler, T. A., Sowa, M. E., Bennett, E. J., Richter, C. M., Tyler, R. E., Greenblatt, E. J., Harper, J. W., & Kopito, R. R. (2011) · Nature Cell Biology · doi:10.1038/ncb2383 · Cited by 470 · cited 2× · see citing works
“Loss of the EMC in mammalian cells is associated with failed biogenesis and degradation of a subset of membrane proteins (Christianson et al., 2012).”
BackgroundMethodEmerging Diversity in Lipid–Protein Interactions
Corradi, V., Sejdiu, B. I., Galloso, H. M., Abdizadeh, H., Noskov, S. Y., Marrink, . J., & Tieleman, D. P. (2019) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00451 · Cited by 458 · see citing works
Mitra, K., Ubarretxena-Belandia, I., Taguchi, T., Warren, G., & Engelman, D. (2004) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0307332101 · Cited by 451 · cited 3× · see citing works
“The respective distance from the cytoplasmic EMC2 N-terminus to the lumenal side of the lipid-filled cavity is approximately 35 Å across, which is close to the average ER membrane thickness (Mitra et al., 2004).”
BackgroundIdentification of Zika Virus and Dengue Virus Dependency Factors using Functional Genomics
Savidis, G., McDougall, W. M., Meraner, P., Perreira, J. M., Portmann, J. M., Trincucci, G., John, S. P., Aker, A. M., Renzette, N., Robbins, D. R., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.06.028 · Cited by 353 · see citing works
Valafar, H. (2020) · Biological Language Model · doi:10.1002/9780470020036.ch6 · Cited by 344
Activation of the Unfolded Protein Response by Lipid Bilayer Stress.
Halbleib, K., Pesek, K., Covino, R., Hofbauer, H. F., Wunnicke, D., Hänelt, I., Hummer, G., & Ernst, R. (2017) · Molecules and Cells · doi:10.1016/j.molcel.2017.06.012 · Cited by 333 · cited 1× · see citing works
“Notably, several other membrane proteins involved in ER homeostasis, including Opi1 and Ire1, also contain amphipathic helices that have been proposed to sense the properties of the lipid bilayer (Volmer et al., 2013; Jacquemyn et al., 2017; Halbleib et al., 2017; Hofbauer et al., 2018; Cho et al., 2019).”
BackgroundbiGBac enables rapid gene assembly for the expression of large multisubunit protein complexes
Weissmann, F., Petzold, G., Vanderlinden, R., Veld, P. J. H. I. '., Brown, N., Lampert, F., Westermann, S., Stark, H., Schulman, B., & Peters, J. (2016) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1604935113 · Cited by 328 · see citing works
Self-citationCryo-EM structure of the human α1β3γ2 GABAA receptor in a lipid bilayer
Laverty, D., Desai, R., Uchański, T., Masiulis, S., Stec, W. J., Malinauskas, T., Zivanov, J., Pardon, E., Steyaert, J., Miller, K. W., et al. (2019) · Nature · doi:10.1038/s41586-018-0833-4 · Cited by 316 · see citing works
Lahiri, S., Chao, J. T., Tavassoli, S., Wong, A. K. O., Choudhary, V., Young, B. P., Loewen, C. J. R., & Prinz, W. A. (2014) · PLoS Biology · doi:10.1371/journal.pbio.1001969 · Cited by 306 · cited 1× · see citing works
“, 2009) and these disparate interdependencies have been subsequently observed in numerous species including human EMC (Lahiri et al., 2014; Tang et al., 2017; Guna et al., 2018; Volkmar et al., 2019; Volkmar and Christianson, 2020).”
BackgroundThe ins and outs of endoplasmic reticulum‐controlled lipid biosynthesis
Jacquemyn, J., Cascalho, A. C. C., & Goodchild, R. E. (2017) · EMBO Reports · doi:10.15252/embr.201643426 · Cited by 289 · cited 1× · see citing works
“Notably, several other membrane proteins involved in ER homeostasis, including Opi1 and Ire1, also contain amphipathic helices that have been proposed to sense the properties of the lipid bilayer (Volmer et al., 2013; Jacquemyn et al., 2017; Halbleib et al., 2017; Hofbauer et al., 2018; Cho et al., 2019).”
BackgroundThe ER membrane protein complex is a transmembrane domain insertase
Guna, A., Volkmar, N., Christianson, J. C., & Hegde, R. S. (2017) · Science · doi:10.1126/science.aao3099 · Cited by 283 · see citing works
Abu-Safieh, L., Alrashed, M., Anazi, S., Alkuraya, H., Khan, A. O., Al-Owain, M., Al-Zahrani, J., Al-Abdi, L., Hashem, M., Al-Tarimi, S., et al. (2013) · Genome Research · doi:10.1101/gr.144105.112 · Cited by 276 · see citing works
Marinko, J. T., Huang, H., Penn, W. D., Capra, J. A., Schlebach, J. P., & Sanders, C. R. (2019) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00532 · Cited by 249 · cited 1× · see citing works
“and this can lead to cellular stress and disease (Marinko et al., 2019).”
BackgroundEMC Is Required to Initiate Accurate Membrane Protein Topogenesis
Chitwood, P. J., Juszkiewicz, S., Guna, A., Shao, S., & Hegde, R. S. (2018) · Cell · doi:10.1016/j.cell.2018.10.009 · Cited by 216 · cited 24× · see citing works
“Here, mutating interfacial residues from EMC5 (EMC5H19L+S23A+Q26L) caused a marked decrease in the N-lumenal polytopic reporter (B1AR) and a mild decrease in the tail-anchored client (SQS) with no effect on the TMEM97 reporter (Figure 6F).”
BackgroundResultInfluentialDefining the physiological role of SRP in protein-targeting efficiency and specificity
Boydston, E. A., Subramanian, K., Nunnari, J. M., & Weissman, J. S. (2018) · Science · doi:10.1126/science.aar3607 · Cited by 216 · see citing works
Self-citationShurtleff, M. J., Itzhak, D. N., Hussmann, J. A., Oakdale, N. T. S., Boydston, E. A., Jonikas, M. C., Weibezahn, J., Popova, K. D., Jan, C. H., Sinitcyn, P. G., et al. (2018) · eLife · doi:10.7554/elife.37018 · Cited by 211 · see citing works
Self-citationA genome-wide atlas of co-essential modules assigns function to uncharacterized genes
Wainberg, M., Kamber, R. A., Balsubramani, A., Meyers, R. M., Sinnott-Armstrong, N., Hornburg, D., Jiang, L., Chan, J., Jian, R., Gu, M., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00840-z · Cited by 204 · see citing works
Focus: The interface between data collection and data processing in cryo-EM.
Biyani, N., Righetto, R., McLeod, R., Caujolle-Bert, D., Castaño-Díez, D., Goldie, K., & Stahlberg, H. (2017) · Journal of Structural Biology · doi:10.1016/j.jsb.2017.03.007 · Cited by 203 · cited 6× · see citing works
“Cryo-EM data processing for hEMC in detergent Preprocessing in Focus included dose-weighted motion correction using Motioncor2 (Zheng, 2017), CTF estimation using Gctf (Zhang, 2016) and templated autopicking using Gautomatch (Kai Zhang).”
MethodInfluentialHagn, F., Nasr, M., & Wagner, G. (2017) · Nature Protocols · doi:10.1038/nprot.2017.094 · Cited by 180 · cited 1× · see citing works
“coli following a published protocol (Hagn et al., 2018).”
Fabs Enable Single Particle cryoEM Studies of Small Proteins
Wu, S., Avila-Sakar, A., Kim, J., Booth, D. S., Greenberg, C. H., Rossi, A., Liao, M., Li, X., Alian, A., Griner, S. L., et al. (2012) · Structure · doi:10.1016/j.str.2012.02.017 · Cited by 178 · see citing works
Self-citationStructural basis for membrane insertion by the human ER membrane protein complex
Pleiner, T., Tomaleri, G. P., Januszyk, K., Inglis, A. J., Hazu, M., & Voorhees, R. M. (2020) · Science · doi:10.1126/science.abb5008 · Cited by 161 · see citing works
Identification of Oxa1 homologs operating in the eukaryotic endoplasmic reticulum.
Anghel, S. A., McGilvray, P. T., Hegde, R. S., & Keenan, R. J. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.12.006 · Cited by 150 · see citing works
Cryo–electron microscopy structures of human oligosaccharyltransferase complexes OST-A and OST-B
Ramírez, A., Kowal, J., & Locher, K. (2019) · Science · doi:10.1126/science.aaz3505 · Cited by 147
Co‐ and Post‐Translational Protein Folding in the ER
Ellgaard, L., McCaul, N., Chatsisvili, A., & Braakman, I. (2016) · Traffic · doi:10.1111/tra.12392 · Cited by 147 · see citing works
Dissecting the molecular organization of the translocon-associated protein complex
Pfeffer, S., Dudek, J., Schaffer, M., Ng, B., Albert, S., Plitzko, J., Baumeister, W., Zimmermann, R., Freeze, H., Engel, B., et al. (2017) · Nature Communications · doi:10.1038/ncomms14516 · Cited by 146 · cited 1× · see citing works
“Compared to other ER-resident proteins implicated in membrane protein biogenesis (Suloway et al., 2009; Pfeffer et al., 2017; Ramı́rez et al., 2019; McDowell et al., 2020; McGilvray et al., 2020), the arrangement of domains of the EMC is unusual with the transmembrane domain connecting prominent cytoplasmic and lumena…”
BackgroundCrystal structure of Escherichia coli YidC, a membrane protein chaperone and insertase
Kumazaki, K., Kishimoto, T., Furukawa, A., Mori, H., Tanaka, Y., Dohmae, N., Ishitani, R., Tsukazaki, T., & Nureki, O. (2014) · Scientific Reports · doi:10.1038/srep07299 · Cited by 142 · see citing works
An ER translocon for multi-pass membrane protein biogenesis
McGilvray, P. T., Anghel, S. A., Sundaram, A., Zhong, F. W., Trnka, M. J., Fuller, J. R., Hu, H., Burlingame, A. L., & Keenan, R. J. (2020) · eLife · doi:10.7554/elife.56889 · Cited by 135 · cited 2× · see citing works
“Compared to other ER-resident proteins implicated in membrane protein biogenesis (Suloway et al., 2009; Pfeffer et al., 2017; Ramı́rez et al., 2019; McDowell et al., 2020; McGilvray et al., 2020), the arrangement of domains of the EMC is unusual with the transmembrane domain connecting prominent cytoplasmic and lumena…”
BackgroundStructure of the ER membrane complex, a transmembrane-domain insertase
Bai, L., You, Q., Feng, X., Kovach, A., & Li, H. (2020) · Nature · doi:10.1038/s41586-020-2389-3 · Cited by 134 · cited 5× · see citing works
“recent studies (O’Donnell et al., 2020; Pleiner et al., 2020; Bai et al., 2020), suggest that clients”
BackgroundResultInfluentialRichard, M., Boulin, T., Robert, V. J. P., Richmond, J. E., & Bessereau, J. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1216154110 · Cited by 114 · see citing works
Satoh, T., Ohba, A., Liu, Z., Inagaki, T., & Satoh, A. K. (2015) · eLife · doi:10.7554/elife.06306 · Cited by 113 · see citing works
Assimon, V. A., Southworth, D. R., & Gestwicki, J. E. (2015) · Biochemistry · doi:10.1021/acs.biochem.5b00801 · Cited by 112 · see citing works
Lin, D. L., Inoue, T., Chen, Y., Chang, A., Tsai, B., & Tai, A. W. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.04.051 · Cited by 105 · see citing works
Vyas, N., Vyas, M. N., Chervenak, M. C., Johnson, M. A., Pinto, B., Bundle, D. R., & Quiocho, F. (2002) · Biochemistry · doi:10.1021/bi0261387 · Cited by 103
Volkmar, N., Thezenas, M.-L., Louie, S. M., Juszkiewicz, S., Nomura, D. K., Hegde, R. S., Kessler, B. M., & Christianson, J. C. (2018) · Journal of Cell Science · doi:10.1242/jcs.223453 · Cited by 101 · see citing works
Heberle, F., Doktorova, M., Scott, H. L., Skinkle, A. D., Waxham, M., & Levental, I. (2020) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1101/2020.02.05.935551 · Cited by 101 · see citing works
The architecture of EMC reveals a path for membrane protein insertion
O'Donnell, J., Phillips, B., Yagita, Y., Juszkiewicz, S., Wagner, A., Malinverni, D., Keenan, R., Miller, E., & Hegde, R. (2020) · bioRxiv · doi:10.1101/2020.05.15.098574 · Cited by 99
Lipid-Protein Interactions Are a Unique Property and Defining Feature of G Protein-Coupled Receptors
Sejdiu, B. I., & Tieleman, D. P. (2020) · Biophysical Journal · doi:10.1016/j.bpj.2020.03.008 · Cited by 98 · see citing works
SMP-domain proteins at membrane contact sites: Structure and function
Reinisch, K. M., & Camilli, P. V. D. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2015.12.003 · Cited by 94 · see citing works
Structural Basis of Tail-Anchored Membrane Protein Biogenesis by the GET Insertase Complex.
McDowell, M. A., Heimes, M., Fiorentino, F., Mehmood, S., Farkas, Á., Coy-Vergara, J., Wu, D., Bolla, J., Schmid, V., Heinze, R. J., et al. (2020) · Molecules and Cells · doi:10.1016/j.molcel.2020.08.012 · Cited by 87 · cited 2× · see citing works
“Compared to other ER-resident proteins implicated in membrane protein biogenesis (Suloway et al., 2009; Pfeffer et al., 2017; Ramı́rez et al., 2019; McDowell et al., 2020; McGilvray et al., 2020), the arrangement of domains of the EMC is unusual with the transmembrane domain connecting prominent cytoplasmic and lumena…”
BackgroundMitigating local over-fitting during single particle reconstruction with SIDESPLITTER
Ramlaul, K., Palmer, C., Nakane, T., & Aylett, C. H. S. (2019) · bioRxiv · doi:10.1016/j.jsb.2020.107545 · Cited by 85 · see citing works
Model for eukaryotic tail-anchored protein binding based on the structure of Get3
Suloway, C. J. M., Chartron, J. W., Zaslaver, M., & Clemons, W. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0907522106 · Cited by 83 · see citing works
Chaudhary, S., Pak, J., Gruswitz, F., Sharma, V., & Stroud, R. (2012) · Nature Protocols · doi:10.1038/nprot.2011.453 · Cited by 83 · cited 2× · see citing works
“Cells were maintained at 37 ̊C in Freestyle 293 Expression Medium (Thermo) and expanded with home-made suspension medium (Chaudhary et al., 2012) in 2 L shaker flasks.”
MethodSelf-citationA yeast phenomic model for the gene interaction network modulating CFTR-ΔF508 protein biogenesis
Louie, R. J., Guo, J., Rodgers, J. W., White, R., Shah, N. A., Pagant, S., Kim, P., Livstone, M. S., Dolinski, K. J., McKinney, B. A., et al. (2012) · Genome Medicine · doi:10.1186/gm404 · Cited by 82 · see citing works
Harel, T., Yeşil, G., Bayram, Y., Coban‐Akdemir, Z., Charng, W., Karaca, E., Asmari, A. A., Eldomery, M. K., Hunter, J. V., Jhangiani, S. N., et al. (2016) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2016.01.011 · Cited by 82 · cited 3× · see citing works
“We investigated several known disease mutations in both conserved and human-specific regions of hEMC1 (Figure 7C–D, Figure 7—figure supplements 2–3; Harel et al., 2016; Abu-Safieh et al., 2013; Amberger et al., 2019).”
BackgroundInfluentialThe ubiquitous and ancient ER membrane protein complex (EMC): tether or not?
Wideman, J. G. (2015) · F1000Research · doi:10.12688/f1000research.6944.2 · Cited by 74 · see citing works
The molecular recognition of phosphatidic acid by an amphipathic helix in Opi1
Hofbauer, H. F., Gecht, M., Fischer, S., Seybert, A., Frangakis, A. S., Stelzer, E. H. K., Covino, R., Hummer, G., & Ernst, R. (2018) · The Journal of Cell Biology · doi:10.1083/jcb.201802027 · Cited by 73 · see citing works
Endoplasmic Reticulum Targeting and Insertion of Tail-Anchored Membrane Proteins by the GET PathwayPreprint
Denic, V., Dötsch, V., & Sinning, I. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a013334 · Cited by 72 · cited 1× · see citing works
“yeast) or WRB (in human) complexes (Denic et al., 2013; Mateja and Keenan, 2018).”
A YidC-like protein in the archaeal plasma membrane.
Borowska, M. T., Dominik, P. K., Anghel, S. A., Kossiakoff, A. A., & Keenan, R. J. (2015) · Structure · doi:10.1016/j.str.2015.06.025 · Cited by 71 · cited 2× · see citing works
“One EMC subunit (EMC3) shares limited sequence homology with a family of insertases that are evolutionarily related to the bacterial insertase YidC (Samuelson, 2000; Kumazaki, 2014; Borowska, 2015; Anghel, 2017), perhaps explaining the insertase function of the complex.”
BackgroundResLog Plots as an Empirical Metric of the Quality of Cryo-EM Reconstructions
Stagg, S., Noble, A., Spilman, M. S., & Chapman, M. (2013) · Journal of Structural Biology · doi:10.1016/j.jsb.2013.12.010 · Cited by 71 · see citing works
Ngo, A. M., Shurtleff, M. J., Popova, K. D., Kulsuptrakul, J., Weissman, J., & Puschnik, A. (2019) · bioRxiv · doi:10.1101/572602 · Cited by 66
Self-citationProteomic Analysis Identifies Membrane Proteins Dependent on the ER Membrane Protein Complex
Tian, S., Wu, Q., Zhou, B. O., Choi, M. Y., Ding, B., Yang, W., & Dong, M. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.08.006 · Cited by 66 · see citing works
Direct imaging of liquid domains in membranes by cryo-electron tomography
Cornell, C., Mileant, A., Thakkar, N., Lee, K. K., & Keller, S. (2020) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1101/2020.02.05.935684 · Cited by 65 · cited 1×
“This dimension exceeds the thickness of the ER membrane (Mitra, 2004; Heberle, 2020; Cornell, 2020) (Figure 4D).”
BackgroundSlp1-Emp65: A Guardian Factor that Protects Folding Polypeptides from Promiscuous Degradation
Zhang, S., Xu, C., Larrimore, K. E., & Ng, D. (2017) · Cell · doi:10.1016/j.cell.2017.08.036 · Cited by 63 · see citing works
The Tetratricopeptide Repeats of Receptors Involved in Protein Translocation across Membranes
Schlegel, T., Mirus, O., von Haeseler, A., & Schleiff, E. (2007) · Molecular Biology and Evolution · doi:10.1093/molbev/msm211 · Cited by 62 · see citing works
Secretory pathway genes assessed by high-throughput microscopy and synthetic genetic array analysis
Bircham, P. W., Maass, D. R., Roberts, C. A., Kiew, P. Y., Low, Y. S., Yegambaram, M., Matthews, J., Jack, C., & Atkinson, P. H. (2011) · Molecular BioSystems · doi:10.1039/c1mb05175j · Cited by 59 · cited 1× · see citing works
“Mutations in this lumenal domain have been linked to loss of the EMC complex (Bircham et al., 2011), a trafficking delay for membrane protein Pma1 (Luo et al.”
BackgroundTMEM16K is an interorganelle regulator of endosomal sorting
Petkovic, M., Oses-Prieto, J., Burlingame, A., Jan, L., & Jan, Y. (2020) · Nature Communications · doi:10.1038/s41467-020-17016-8 · Cited by 56
EMC3 coordinates surfactant protein and lipid homeostasis required for respiration
Tang, X., Snowball, J., Xu, Y., Na, C.-L., Weaver, T., Clair, G., Kyle, J., Zink, E. M., Ansong, C., Wei, W., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci94152 · Cited by 55
Lipids Alter Rhodopsin Function via Ligand-like and Solvent-like Interactions
Salas-Estrada, L. A., Leioatts, N., Romo, T. D., & Grossfield, A. M. (2018) · Biophysical Journal · doi:10.1016/j.bpj.2017.11.021 · Cited by 53 · see citing works
Bagchi, P., Inoue, T., & Tsai, B. (2016) · eLife · doi:10.7554/elife.21470 · Cited by 52 · see citing works
A particle-filter framework for robust cryo-EM 3D reconstruction
Hu, M., Yu, H.-K., Gu, K., Wang, Z., Ruan, H., Wang, K., Ren, S., Li, B., Gan, L., Xu, S.-Z., et al. (2018) · Nature Methods · doi:10.1038/s41592-018-0223-8 · Cited by 51 · see citing works
Cho, H., Stanzione, F., Oak, A., Kim, G., Yerneni, S., Qi, L., Sum, A., & Chan, C. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.03.017 · Cited by 50
Volkmar, N., & Christianson, J. C. (2020) · Journal of Cell Science · doi:10.1242/jcs.243519 · Cited by 48 · see citing works
A structural perspective on tail-anchored protein biogenesis by the GET pathway
Mateja, A., & Keenan, R. J. (2018) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2018.07.009 · Cited by 47 · see citing works
A network of chaperones prevents and detects failures in membrane protein lipid bilayer integration
Coelho, J. P. L., Stahl, M., Bloemeke, N., Meighen-Berger, K. M., Alvira, C. P., Zhang, Z.-R., Sieber, S., & Feige, M. (2019) · Nature Communications · doi:10.1038/s41467-019-08632-0 · Cited by 44 · cited 3×
“strate-specific chaperones in the cytoplasm and in the ER lumen (Bagchi et al., 2016; Coelho et al., 2019; Kudze et al., 2018; Richard et al., 2013; Shurtleff et al., 2018).”
BackgroundTalbot, B. E., Vandorpe, D. H., Stotter, B. R., Alper, S. L., & Schlöndorff, J. S. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.008299 · Cited by 43 · see citing works
Diamantopoulou, A., Sun, Z., Mukai, J., Xu, B., Fénelon, K., Karayiorgou, M., & Gogos, J. A. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1615719114 · Cited by 41 · see citing works
Rapid identification of recombinant Fabs that bind to membrane proteins
Kim, J., Stroud, R., & Craik, C. (2011) · Methods · doi:10.1016/j.ymeth.2011.09.012 · Cited by 40 · cited 2×
“Fabs were identified as described in these studies (Kim et al., 2011; Wu et al., 2012).”
BackgroundMethodSelf-citationXiong, L., Zhang, L., Yang, Y., Li, N., Lai, W., Wang, F., Zhu, X., & Wang, T. (2019) · Cell Death and Differentiation · doi:10.1038/s41418-019-0378-6 · Cited by 36 · see citing works
TPR-containing proteins control protein organization and homeostasis for the endoplasmic reticulum
Graham, J. B., Canniff, N. P., & Hebert, D. N. (2019) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2019.1590305 · Cited by 30 · see citing works
An ER Membrane Protein, Sop4, Facilitates ER Export of the Yeast Plasma Membrane [H+]ATPase, Pma1
Luo, W.-J., Gong, X., & Chang, A. (2002) · Traffic : the International Journal of Intracellular Transport · doi:10.1034/j.1600-0854.2002.31005.x · Cited by 30
EMC10 governs male fertility via maintaining sperm ion balance
Zhou, Y., Wu, F., Zhang, M., Xiong, Z., Yin, Q., Ru, Y., Shi, H., Li, J., Mao, S., Li, Y., et al. (2018) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjy024 · Cited by 29 · see citing works
Disrupted ER membrane protein complex-mediated topogenesis drives congenital neural crest defects.
Marquez, J., Criscione, J., Charney, R. M., Prasad, M. S., Hwang, W., Mis, E., García-Castro, M., & Khokha, M. (2020) · Journal of Clinical Investigation · doi:10.1172/jci129308 · Cited by 29 · see citing works
Structure and Interactions of the TPR Domain of Sgt2 with Yeast Chaperones and Ybr137wp
Krysztofinska, E., Evans, N., Thapaliya, A., Murray, J., Morgan, R. M., Martínez-Lumbreras, S., & Isaacson, R. (2017) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2017.00068 · Cited by 24 · see citing works
Membrane Insertases Are Present in All Three Domains of Life
Dalbey, R., & Kühn, A. (2015) · Structure · doi:10.1016/j.str.2015.08.002 · Cited by 19 · see citing works
hHSS1: a novel secreted factor and suppressor of glioma growth located at chromosome 19q13.33
Junes-Gill, K. S., Gallaher, T., Gluzman-Poltorak, Z., Miller, J. D., Wheeler, C., Fan, X., & Basile, L. (2010) · Journal of Neuro-Oncology · doi:10.1007/s11060-010-0314-6 · Cited by 19 · see citing works
Hiramatsu, N., Tago, T., Satoh, T., & Satoh, A. K. (2019) · Molecular Biology of the Cell · doi:10.1091/mbc.e19-08-0434 · Cited by 15 · see citing works
Evidence for interaction between Hsp90 and the ER membrane complex
Kudze, T., Mendez‐Dorantes, C., Jalloh, S., & McClellan, A. J. (2018) · Cell Stress and Chaperones · doi:10.1007/s12192-018-0908-z · Cited by 12 · cited 1× · see citing works
“strate-specific chaperones in the cytoplasm and in the ER lumen (Bagchi et al., 2016; Coelho et al., 2019; Kudze et al., 2018; Richard et al., 2013; Shurtleff et al., 2018).”
Background1H NMR Metabolic Profiling of Plasma Reveals Additional Phenotypes in Knockout Mouse Models
Probert, F., Rice, P., Scudamore, C. L., Wells, S. E., Williams, R. L., Hough, T., & Cox, I. J. (2015) · Journal of Proteome Research · doi:10.1021/pr501039k · Cited by 11 · see citing works
The hybridoma revolution: an offshoot of basic research
Milstein, C. (1999) · BioEssays · doi:10.1002/(sici)1521-1878(199911)21:11 · Cited by 9 · see citing works
Millán, J. (2006) · doi:10.1002/3527608060.ch8 · Cited by 9
Ito, K. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.732369786.793568677
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The mechanisms of integral membrane protein biogenesis
Hegde, R. S., & Keenan, R. J. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00413-2 · Cited by 244 · see citing works
Ins and outs of AlphaFold2 transmembrane protein structure predictions
Hegedűs, T., Geisler, M., Lukács, G. L., & Farkas, B. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-04112-1 · Cited by 127 · see citing works
MTCH2 is a mitochondrial outer membrane protein insertase
Guna, A., Stevens, T. A., Inglis, A. J., Replogle, J. M., Esantsi, T. K., Muthukumar, G., Shaffer, K. C. L., Wang, M. L., Pogson, A. N., Jones, J. J., et al. (2022) · Science · doi:10.1126/science.add1856 · Cited by 143 · see citing works
Self-citationSubstrate-driven assembly of a translocon for multipass membrane proteins
Sundaram, A., Yamsek, M., Zhong, F. W., Hooda, Y., Hegde, R. S., & Keenan, R. J. (2022) · Nature · doi:10.1038/s41586-022-05330-8 · Cited by 106 · see citing works
“In eukaryotes lacking some or all of the multipass components, the widely conserved EMC 31 may play a more central role in multipass protein biogenesis 20,32–34 .”
A concise guide to choosing suitable gene expression systems for recombinant protein production
Schütz, A., Bernhard, F., Berrow, N., Buyel, J., Ferreira-da-Silva, F., Haustraete, J., van den Heuvel, J., Hoffmann, J.-E., de Marco, A., Peleg, Y., et al. (2023) · STAR Protocols · doi:10.1016/j.xpro.2023.102572 · Cited by 87
“66 Different molecular cloning technologies—Golden Gate (GoldenBac), 67 Gibson assembly of PCR fragments (biGBac), 65 Cre-lox recombination (MultiBac) 68 —allow efficient multi-gene assembly in the baculovirus genome (see Table S2).”
BackgroundLiaci, A. M., & Förster, F. G. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222111871 · Cited by 78 · see citing works
Structural and molecular mechanisms for membrane protein biogenesis by the Oxa1 superfamily.
McDowell, M. A., Heimes, M., & Sinning, I. (2021) · Nature Structural & Molecular Biology · doi:10.1038/s41594-021-00567-9 · Cited by 66 · see citing works
Müller, M. B. D., Kasturi, P., Jayaraj, G. G., & Hartl, F. U. (2023) · Cell · doi:10.1016/j.cell.2023.05.035 · Cited by 78 · see citing works
Translocation of proteins through a distorted lipid bilayer
Wu, X., & Rapoport, T. (2021) · Trends in Cell Biology · doi:10.1016/j.tcb.2021.01.002 · Cited by 65 · see citing works
EMC chaperone–CaV structure reveals an ion channel assembly intermediate
Chen, Z., Mondal, A., Abderemane-Ali, F., Jang, S., Niranjan, S., Montaño, J. L., Zaro, B. W., & Minor, D. L. (2023) · Nature · doi:10.1038/s41586-023-06175-5 · Cited by 81 · see citing works
Highlighting membrane protein structure and function: A celebration of the Protein Data Bank
Li, F., Egea, P. F., Vecchio, A. J., Asial, I., Gupta, M., Paulino, J., Bajaj, R., Dickinson, M. S., Ferguson-Miller, S. M., Monk, B. C., et al. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100557 · Cited by 81 · see citing works
Self-citationThe function, structure, and origins of the ER membrane protein complex
Hegde, R. S. (2022) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-032620-104553 · Cited by 61 · see citing works
“A gate containing EMC4 is proposed to open in response to substrate binding, allowing the substrate’s hydrophilic flanking domain to enter EMC’s hydrophilic vestibule.”
InfluentialStructural biology of voltage-gated calcium channels
Yao, X., Gao, S., & Yan, N. (2023) · Channels · doi:10.1080/19336950.2023.2290807 · Cited by 48 · see citing works
“Various structural and mutagenesis studies have outlined the functional roles of the EMC and implied diverse interactions with client proteins [89][90][91].”
BackgroundAn alternative pathway for membrane protein biogenesis at the endoplasmic reticulum
O’Keefe, S. M., Zong, G., Duah, K. B., Andrews, L. E., Shi, W. Q., & High, S. (2021) · Communications Biology · doi:10.1038/s42003-021-02363-z · Cited by 65 · see citing works
Membrane protein biogenesis at the ER: the highways and byways
O’Keefe, S. M., Pool, M., & High, S. (2021) · FEBS Journal · doi:10.1111/febs.15905 · Cited by 52 · see citing works
Capture and delivery of tail-anchored proteins to the endoplasmic reticulum
Farkas, Á., & Bohnsack, K. (2021) · Journal of Cell Biology · doi:10.1083/jcb.202105004 · Cited by 41 · see citing works
“In yeast, Get4-Get5 form an obligate heterodimer, whereas the homologous TRC35 and UBL4A interact via an additional component BAG6 (Chang et al., 2010; Chartron et al., 2010; Mariappan et al., 2010; Mock et al., 2015).”
BackgroundA unifying model for membrane protein biogenesis
Hegde, R. S., & Keenan, R. J. (2024) · Nature Structural & Molecular Biology · doi:10.1038/s41594-024-01296-5 · Cited by 41 · see citing works
“…diverse Oxa1 family members in bacteria, archaea, endosymbiont organelle inner membranes and the ER show a cytosol-facing hydrophilic vestibule that would lower the barrier for translocation of short domains, but no channel that could support translocation of long domains 7,19,20,22,46,48,51–57 .”
BackgroundEMC rectifies the topology of multipass membrane proteins
Wu, H.-X., Smalinskaitė, L., & Hegde, R. (2023) · Nature Structural & Molecular Biology · doi:10.1038/s41594-023-01120-6 · Cited by 38 · see citing works
“EMC uses a cytosol-facing hydrophilic vestibule and membrane-embedded hydrophilic groove, both housed primarily in EMC3, to facilitate translocation of a flanking hydrophilic segment concomitant with TMD insertion 7,19,21,23 .”
BackgroundMechanism of signal-anchor triage during early steps of membrane protein insertion
Wu, H., & Hegde, R. S. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.01.018 · Cited by 39 · see citing works
WNK1 is an assembly factor for the human ER membrane protein complex
Pleiner, T., Hazu, M., Tomaleri, G. P., Januszyk, K., Oania, R. S., Sweredoski, M. J., Moradian, A., Guna, A., & Voorhees, R. M. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.04.013 · Cited by 40 · see citing works
A unified evolutionary origin for the ubiquitous protein transporters SecY and YidC
Lewis, A. J. O., & Hegde, R. S. (2021) · BMC Biology · doi:10.1186/s12915-021-01171-5 · Cited by 43 · see citing works
The Biogenesis of Multipass Membrane ProteinsPreprint
Smalinskaitė, L., & Hegde, R. S. (2022) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a041251 · Cited by 42 · see citing works
Targeting of Proteins for Translocation at the Endoplasmic Reticulum
Pool, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23073773 · Cited by 40 · see citing works
Membrane protein folding and quality control
Phillips, B., & Miller, E. (2021) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2021.03.003 · Cited by 28
Tirincsi, A., Sicking, M., Hadzibeganovic, D., Haßdenteufel, S., & Lang, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms23010143 · Cited by 30 · see citing works
A selectivity filter in the ER membrane protein complex limits protein misinsertion at the ER
Pleiner, T., Hazu, M., Tomaleri, G. P., Nguyen, V. N., Januszyk, K., & Voorhees, R. M. (2023) · The Journal of Cell Biology · doi:10.1083/jcb.202212007 · Cited by 33 · see citing works
A toolbox for systematic discovery of stable and transient protein interactors in baker's yeast
Fenech, E. J., Cohen, N., Kupervaser, M., Gazi, Z., & Schuldiner, M. (2023) · Molecular Systems Biology · doi:10.15252/msb.202211084 · Cited by 27 · see citing works
“…et al , 2018; Volkmar et al , 2019), it has also been found to insert multi-pass transmembrane domain (TMD)-containing proteins into the ER (Chitwood et al , 2018; Shurtleff et al , 2018; Tian et al , 2019; Bai et al , 2020; Miller-Vedam et al , 2020; O’Donnell et al , 2020; Pleiner et al , 2020).”
BackgroundER membrane complex (EMC): Structure, functions, and roles in diseases
Zhu, Q., Zhu, X., & Zhang, L. (2024) · The FASEB Journal · doi:10.1096/fj.202302266r · Cited by 13 · see citing works
Co-translational biogenesis of lipid droplet integral membrane proteins
Leznicki, P., Schneider, H. O., Harvey, J. V., Shi, W. Q., & High, S. (2021) · bioRxiv · doi:10.1101/2021.08.05.455205 · Cited by 18
“…the ability of the EMC to translocate both N-terminal and C-terminal segments of hydrophilic polypeptide that are adjacent to a hydrophobic transmembrane region (Bai et al., 2020; Chitwood et al., 2018; Guna et al., 2018; Miller-Vedam et al., 2020; O’Donnell et al., 2020; Pleiner et al., 2020).”
Expulsion mechanism of the substrate-translocating subunit in ECF transporters
Thangaratnarajah, C., Nijland, M., Borges-Araújo, L., Jeucken, A., Rheinberger, J., Marrink, . J., Souza, P. C. T., Paulino, C., & Slotboom, D. J. (2023) · Nature Communications · doi:10.1038/s41467-023-40266-1 · Cited by 17 · see citing works
Coukos, R., Yao, D., Sánchez, M. I., Strand, E. T., Olive, M. E., Udeshi, N. D., Weissman, J. S., Carr, S. A., Bassik, M. C., & Ting, A. Y. (2021) · eLife · doi:10.7554/elife.69142 · Cited by 21 · see citing works
Self-citationHorn‐Ghetko, D., Hopf, L. V. M., Tripathi‐Giesgen, I., Du, J., Kostrhon, S., Vu, D. T., Beier, V., Steigenberger, B. A., Prabu, J. R., Stier, L. J., et al. (2024) · Nature Structural & Molecular Biology · doi:10.1038/s41594-024-01257-y · Cited by 18 · see citing works
Self-citationGlobal analysis of translocon remodeling during protein synthesis at the ER
Sundaram, A., Li, Q.-R., Wan, Y., Tang, J., Wu, H.-X., Smalinskaitė, L., Hegde, R., Ji, Z., & Keenan, R. J. (2025) · Nature Structural & Molecular Biology · doi:10.1038/s41594-025-01691-6 · Cited by 14
“These exposed substrate TMDs would presumably be shielded by general or client-specific intramembrane chaperones such as EMC 36–38 , Nacho 39 or other factors.”
Role of a holo-insertase complex in the biogenesis of biophysically diverse ER membrane proteins
Page, K. R., Nguyen, V. N., Pleiner, T., Tomaleri, G. P., Wang, M. L., Guna, A., Hazu, M., Wang, T., Chou, T., & Voorhees, R. M. (2024) · Molecular Cell · doi:10.1016/j.molcel.2024.08.005 · Cited by 25 · see citing works
Membrane insertases at a glance
Kizmaz, B., & Herrmann, J. M. (2023) · Journal of Cell Science · doi:10.1242/jcs.261219 · Cited by 25 · see citing works
Ending a bad start: Triggers and mechanisms of co-translational protein degradation
Eisenack, T., & Trentini, D. B. (2023) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.1089825 · Cited by 11 · see citing works
“…expressed and highly abundant 10 subunit protein complex that can act as a co-translational membrane insertase for specific protein topologies and as a potential chaperone for transmembrane segments (Chitwood et al., 2018; Guna et al., 2018; Shurtleff et al., 2018; Miller-Vedam et al., 2020).”
BackgroundYidC as a potential antibiotic target
Dalbey, R., Kaushik, S., & Kühn, A. (2022) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2022.119403 · Cited by 14 · see citing works
Chung, H.-L., Rump, P., Lu, D., Glassford, M. R., Mok, J.-W., Fatih, J. M., Basal, A., Marcogliese, P. C., Kanca, O., Rapp, M., et al. (2022) · Human Molecular Genetics · doi:10.1093/hmg/ddac053 · Cited by 16 · see citing works
Porter, S. S., Gilchrist, T. M., Schrodel, S., & Tai, A. W. (2024) · Journal of Virology · doi:10.1128/jvi.01443-24 · Cited by 12 · see citing works
“The EMC has been proposed to function as a chaperone for proteins with complex or weakly hydrophobic transmembrane domains (6, 7).”
Cryo-EM insights into tail-anchored membrane protein biogenesis in eukaryotes.
Sinning, I., & McDowell, M. A. (2022) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2022.102428 · Cited by 12
Malwal, S. R., Shang, N., Liu, W.-D., Li, X., Zhang, L., Chen, C.-C., Guo, R., & Oldfield, E. (2022) · ACS Omega · doi:10.1021/acsomega.2c01924 · Cited by 12 · see citing works
EMC is required for biogenesis of Xport‐A, an essential chaperone of Rhodopsin‐1 and the TRP channel
Gaspar, C. J., Vieira, L., Santos, C. C., Christianson, J. C., Jakubec, D., Střı́šovský, K., Adrain, C., & Domingos, P. M. D. N. (2021) · EMBO Reports · doi:10.15252/embr.202153210 · Cited by 15 · see citing works
Cryo‐EM structures of the endoplasmic reticulum membrane complex
Bai, L., & Li, H. (2021) · FEBS Journal · doi:10.1111/febs.15786 · Cited by 10 · see citing works
Shaping the composition of the mitochondrial outer membrane
Muthukumar, G., & Weissman, J. S. (2025) · Nature Cell Biology · doi:10.1038/s41556-025-01683-0 · Cited by 13 · see citing works
“…poly-topic proteins 122 , the GET1/2 complex inserts high-hydrophobicity tail-anchored proteins 123 , the EMC inserts lower hydrophobicity tail-anchored proteins and some polytopic proteins 124 and TMCO1 forms a super complex with SEC61 to help insert poorly hydrophobic polytopic proteins 125 .”
Self-citationStructural insights into human EMC and its interaction with VDAC
Li, M., Zhang, C., Xu, Y., Li, S., Huang, C., Wu, J., & Lei, M. (2024) · Aging · doi:10.18632/aging.205660 · Cited by 7 · see citing works
“The apo structure of human EMC exhibits a tripartite organization, of which the luminal and cytosolic modules are consistent with the recent structures of human EMC (Figure 2A; Supplementary Figure 2) [24– 27].”
The EMC acts as a chaperone for membrane proteins
Klose, C. J., Meighen-Berger, K. M., Kulke, M., Parr, M., Steigenberger, B., Zacharias, M., Frishman, D., & Feige, M. J. (2025) · Nature Communications · doi:10.1038/s41467-025-62109-x · Cited by 7 · see citing works
“EMC1 Cysteines 227 ↔ 237 and 338 ↔ 368 were oxidized to disul fi de bridges, and β -N-acetylgalactosamin glycosylations were added to EMC1-N370, EMC1-N818, EMC1-N913, and EMC10-N182.”
InfluentialSun, K., Liu, L., Jiang, X., Wang, H., Wang, L., Yang, Y.-M., Liu, W.-J., Zhang, L., Zhao, X., & Zhu, X.-J. (2023) · Genes and Diseases · doi:10.1016/j.gendis.2023.03.033 · Cited by 7 · see citing works
Iyer, A., Niemann, M., Serricchio, M., Dewar, C. E., Oeljeklaus, S., Farine, L., Warscheid, B., Schneider, A., & Bütikofer, P. (2022) · PLoS Pathogens · doi:10.1371/journal.ppat.1009717 · Cited by 10 · see citing works
Ltc1 localization by EMC regulates cell membrane fluidity to facilitate membrane protein biogenesis
Berraquero, M., Tallada, V. A., & Jiménez, J. (2025) · iScience · doi:10.1016/j.isci.2025.112096 · Cited by 6 · see citing works
“50 It is noteworthy that the localization of Ltc1 in contact sites between the ER and the PM and between the ER and the mitochondriadependsontheactivityoftheEMC(seeinFigures3 and 6B).”
Structural insights into the membrane chaperones for multi-pass membrane protein biogenesis
Bai, L., & Li, H. (2023) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2023.102563 · Cited by 6 · see citing works
Yeast as a tool for membrane protein production and structure determination
Carlesso, A., Delgado, R., Isant, O. R., Uwangue, O., Valli, D., Bill, R., & Hedfalk, K. (2022) · FEMS Yeast Research · doi:10.1093/femsyr/foac047 · Cited by 6 · see citing works
Coukos, R., Yao, D., Sánchez, M. I., Strand, E., Weissman, J., Bassik, M., & Ting, A. Y. (2021) · bioRxiv · doi:10.1101/2021.04.11.439362 · Cited by 6
Self-citationShiota, N., Shimokawa-Chiba, N., Fujiwara, K., & Chiba, S. (2023) · Journal of Molecular Biology · doi:10.1016/j.jmb.2023.168172 · Cited by 5 · see citing works
Defining the host dependencies and the transcriptional landscape of RSV infection
Sunshine, S., Puschnik, A., Retallack, H., Laurie, M. T., Liu, J., Peng, D., Knopp, K., Zinter, M., Ye, C., & Derisi, J. (2025) · mBio · doi:10.1128/mbio.01010-25 · Cited by 4
“The EMC complex plays a role in co-translational insertion of transmembrane proteins in the ER, which is a well-appreciated facet of the flavivirus life cycle (44–47).”
Liu, L., Mao, S.-H., Chen, K.-M., Dai, J., Jin, S., Chen, L., Wang, Y.-H., Guo, L., Yang, Y.-T., Zhan, C.-W., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231710069 · Cited by 4 · see citing works
“Structural biology assays show that mEMC10 serves as a lumenal subunit of EMC anchored in the endoplasmic reticulum membrane [7,11].”
BackgroundExpanding EMC Foldopathies: Topogenesis Deficits Alter the Neural Crest
Marquez, J., Aslam, F., & Khokha, M. (2022) · bioRxiv · doi:10.1002/dvg.23520 · Cited by 3 · see citing works
“Our understanding of the EMC has flourished amidst recent studies on the structure, molecular function, and determination of the client proteins of this crucial complex (Chitwood et al. 2018; Guna et al. 2018; Miller-Vedam et al. 2020; O'Donnell et al. 2020; Pleiner et al. 2020; Shurtleff et al. 2018; Tian et al. 2019…”
BackgroundRare among Rare: Phenotypes of Uncommon CMT Genotypes
Gentile, L., Russo, M., Taioli, F., Ferrarini, M., Aguennouz, M., Rodolico, C., Toscano, A., Fabrizi, G., & Mazzeo, A. (2021) · Brain Science · doi:10.3390/brainsci11121616 · Cited by 3
“The hypothesis is that these pathologies are caused by mutations within membrane proteins that require the EMC during their production [49].”
BackgroundGaspar, C. J., Vieira, L., Christianson, J. C., Jakubec, D., Stříšovský, K., Adrain, C., & Domingos, P. M. (2021) · bioRxiv · doi:10.1101/2021.02.01.429115 · Cited by 3
Pairwise transmembrane domain insertion during multipass protein biogenesis
Smalinskaitė, L., Wu, H.-X., & Hegde, R. (2026) · Molecules and Cells · doi:10.1016/j.molcel.2026.06.006 · Cited by 2
Emc1 is essential for vision and zebrafish photoreceptor outer segment morphogenesis
McCann, T., Sundaramurthi, H., Walsh, C. M., Virdi, S., Álvarez, Y. Á., Sapetto-Rebow, B., Collery, R. F., Carter, S. P., Moran, A. L., Mulholland, R., et al. (2024) · The FASEB Journal · doi:10.1096/fj.202401977r · Cited by 3 · see citing works
“42 The majority of disease mutations in humans (marked in green in Figure 5F) are present in the lumenal domain of EMC1 highlighting its crucial role.”
The prolyl isomerase FKBP11 is a secretory translocon accessory factor
DiGuilio, A., Cheng, B., Zhong, F., Jha, R., Wan, Y., Anghel, S. A., Hu, H., Shishkova, E., Ji, Z., Coon, J., et al. (2024) · Molecular Biology of the Cell · doi:10.1091/mbc.e24-07-0305 · Cited by 2
“…cytosolic tail prevents comigration with 80S ribosomes and the Sec61 complex. subunits of the ER membrane protein complex (EMC) (Bai et al. , 2020; Miller-Vedam et al. , 2020; O’Donnell et al. , 2020; Pleiner et al. , 2020), the multipass translocon (MPT) (Chitwood and Hegde, 2020; McGilvray et…”
Myronidi, I., Ring, A., Wú, F., & Ljungdahl, P. O. (2023) · The Journal of Cell Biology · doi:10.1083/jcb.202208060 · Cited by 2 · see citing works
Kalavacherla, T., Buschmann, S., Schleker, E. S. M., Michel, H., & Reinhart, C. (2023) · Protein Expression and Purification · doi:10.1016/j.pep.2023.106230 · Cited by 2 · see citing works
Thielen, A. S., Bräuning, B., Gottemukkala, K. V., Müller, J., Prabu, J. R., Verma, P., Klaessens, S., den Eynde, B. J. V., Kleiger, G., Murray, P. J., et al. (2026) · Molecular Cell · doi:10.1016/j.molcel.2026.09.023
Self-citationThielen, A. S., Bräuning, B., Gottemukkala, K. V., Müller, J., Prabu, J. R., Klaessens, S., den Eynde, B. J. V., Murray, P. J., & Schulman, B. A. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.12.698998
Self-citationChen, Z., & Minor, D. L. (2025) · Biochemical Society Transactions · doi:10.1042/bst20240422 · Cited by 1
Chen, Z., Mondal, A., Abderemane-Ali, F., Moñtano, J. L., Zaro, B. W., & Minor, D. (2022) · bioRxiv · doi:10.1101/2022.10.03.510667 · Cited by 1
Structural analysis of the dynamic ribosome-translocon complex
Lewis, A. J. O., Zhong, F., Keenan, R. J., & Hegde, R. S. (2023) · doi:10.1101/2023.12.22.572959
They grow up so fast – the birth and development of membrane contact site research
Levine, T. P., Loewen, C. J. R., & Prinz, W. A. (2026) · Journal of Cell Science · doi:10.1242/jcs.264796
Structural basis of an endoplasmic reticulum EMC:Spf1 insertase–dislocase complex
Klose, C. J., Prabu, J. R., Fenech, E. J., Bräuning, B., Baydar, I., Steigenberger, B., von Gronau, S., Arad, S., Langlois, C. R., Schuldiner, M., et al. (2026) · Nature Structural & Molecular Biology · doi:10.1038/s41594-026-01883-8
“2b; root-mean-square deviation (r.m.s.d.) to PDB 7KRA: 0.9 Å, r.m.s.d. to PDB 7KTX: 1.1 Å, r.m.s.d. to PDB 6WB9: 1.2 Å) 15,18 .”
InfluentialSelf-citationQiao, Y., Sun, Y., Huang, Y., Meng, Q., Lin, X., Wei, W., & Tang, X. (2026) · Cell Proliferation · doi:10.1111/cpr.70191
Structural basis of an EMC:Spf1 insertase-dislocase complex in the eukaryotic endoplasmic reticulumPreprint
Klose, C. J., Prabu, J. R., Fenech, E. J., Bräuning, B., Baydar, I., Steigenberger, B., von Gronau, S., Arad, S., Langlois, C. R., Schuldiner, M., et al. (2025) · bioRxiv · doi:10.1101/2025.08.07.669073
“Extending this previous work, we resolved additional C-terminal residues for the subunits Emc4, Emc7 (also named Sop4) and Emc10 37,38 .”
InfluentialSelf-citationSunshine, S., Puschnik, A., Retallack, H., Laurie, M. T., Liu, J., Peng, D., Knopp, K., Zinter, M., Ye, C., & Derisi, J. (2025) · bioRxiv · doi:10.1101/2025.03.26.645108
“The EMC complex plays a role in co-translational insertion of transmembrane proteins in the ER, which is a well appreciated facet of the flavivirus life cycle [32–35].”
Awasthi, S., Singh, B., Ramani, V., Godbole, N., & King, C. (2023) · Infection and Immunity · doi:10.1128/iai.00311-23
Li, Y., Shen, R., Cheng, Y.-M., Zhao, Q., Jin, K., Jin, Z., & Zhang, S. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e20146
A selectivity filter in the EMC limits protein mislocalization to the ER
Pleiner, T., Hazu, M., Tomaleri, G. P., Nguyen, V., Januszyk, K., & Voorhees, R. (2022) · bioRxiv · doi:10.1101/2022.11.29.518402
- Authors
- Miller-Vedam, L. E., Bräuning, B., Popova, K. D., Schirle Oakdale, N. T., Bonnar, J. L., Prabu, J. R., Boydston, E. A., Sevillano, N., Shurtleff, M. J., Stroud, R. M., Craik, C. S., Schulman, B. A., Frost, A., & Weissman, J. S.
- Affiliations
- University of California, San Francisco (US)
- Max Planck Institute of Biochemistry (DE)
- Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States
- Howard Hughes Medical Institute (US)
- Corresponding author
- Schulman, Brenda A
- Frost, Adam
- Weissman, Jonathan S
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2020-11-25
- Volume
- 9
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC7785296
- OpenAlex
- W3110296556
- Cited by
- 87
- References
- 148
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 13 · 2023: 21 · 2022: 15 · 2021: 17 · 2020: 2
- FWCI
- 6.86
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- eScholarship (California Digital Library) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Funders
- Deutsche Forschungsgemeinschaft (Leibniz Prize SCHU 3196/1-1)
- Max Planck Society
- National Institutes of Health (P50AI150476, 1P41CA196276-01, 1DP2OD017690-01, GM24485)
- Helen Hay Whitney Foundation
- Peter und Traudl Engelhorn Stiftung
- Jane Coffin Childs Memorial Fund for Medical Research
- Howard Hughes Medical Institute (55108523)
- Chan Zuckerberg Initiative
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- electromagnetic compatibility, membrane protein biogenesis, endoplasmic reticulum, tail-anchored proteins, polytopic membrane proteins, protein insertion
- MeSH terms
- Endoplasmic Reticulum, Humans, Intracellular Membranes, Membrane Proteins, Saccharomyces cerevisiae, Blotting, Western, Sequence Alignment, Protein Structure, Tertiary, Saccharomyces cerevisiae Proteins
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