Evidence for a trap-and-flip mechanism in a proton-dependent lipid transporter
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Abstract
Transport of lipids across membranes is fundamental for diverse biological pathways in cells. Multiple ion-coupled transporters take part in lipid translocation, but their mechanisms remain largely unknown. Major facilitator superfamily (MFS) lipid transporters play central roles in cell wall synthesis, brain development and function, lipids recycling, and cell signaling. Recent structures of MFS lipid transporters revealed overlapping architectural features pointing towards a common mechanism. Here we used cysteine disulfide trapping, molecular dynamics simulations, mutagenesis analysis, and transport assays in vitro and in vivo, to investigate the mechanism of LtaA, a proton-dependent MFS lipid transporter essential for lipoteichoic acid synthesis in the pathogen Staphylococcus aureus . We reveal that LtaA displays asymmetric lateral openings with distinct functional relevance and that cycling through outward- and inward-facing conformations is essential for transport activity. We demonstrate that while the entire amphipathic central cavity of LtaA contributes to lipid binding, its hydrophilic pocket dictates substrate specificity. We propose that LtaA catalyzes lipid translocation by a ‘trap-and-flip’ mechanism that might be shared among MFS lipid transporters.
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VMD: visual molecular dynamics
Humphrey, W., Dalke, A., & Schulten, K. (1996) · Journal of Molecular Graphics · doi:10.1016/0263-7855(96)00018-5 · Cited by 66,952 · see citing works
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764 · see citing works
Comparison of simple potential functions for simulating liquid water
Jorgensen, W. L., Chandrasekhar, J., Madura, J., Impey, R., & Klein, M. (1983) · The Journal of Chemical Physics · doi:10.1063/1.445869 · Cited by 38,335 · see citing works
Molecular dynamics with coupling to an external bath
Berendsen, H. J. C., Postma, J. P. M., van Gunsteren, W. F., DiNola, A., & Haak, J. R. (1984) · The Journal of Chemical Physics · doi:10.1063/1.448118 · Cited by 30,626 · see citing works
Particle mesh Ewald: An N⋅log(N) method for Ewald sums in large systems
Darden, T., York, D., & Pedersen, L. (1993) · The Journal of Chemical Physics · doi:10.1063/1.464397 · Cited by 29,588 · see citing works
Abraham, M. J., Murtola, T., Schulz, R., Páll, S., Smith, J. C., Hess, B., & Lindahl, E. (2015) · SoftwareX · doi:10.1016/j.softx.2015.06.001 · Cited by 27,190 · see citing works
Canonical dynamics: Equilibrium phase-space distributions
Hoover, W. G. (1985) · Physical Review A · doi:10.1103/physreva.31.1695 · Cited by 23,453 · see citing works
Polymorphic transitions in single crystals: A new molecular dynamics method
Parrinello, M., & Rahman, A. (1981) · Journal of Applied Physics · doi:10.1063/1.328693 · Cited by 19,668 · see citing works
LINCS: A linear constraint solver for molecular simulations
Hess, B., Bekker, H., Berendsen, H. J. C., & Fraaije, J. G. E. M. (1997) · Journal of Computational Chemistry · doi:10.1002/(sici)1096-987x(199709)18:12 · Cited by 18,369 · see citing works
<i>MolProbity</i> : all-atom structure validation for macromolecular crystallography
Chen, V. B., Arendall, W. B., Headd, J. J., Keedy, D. A., Immormino, R. M., Kapral, G. J., Murray, L. W., Richardson, J. S., & Richardson, D. C. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909042073 · Cited by 14,115 · see citing works
Friesner, R. A., Banks, J. L., Murphy, R. B., Halgren, T. A., Klicic, J. J., Mainz, D. T., Repasky, M. P., Knoll, E. H., Shelley, M., Perry, J. K., et al. (2004) · Journal of Medicinal Chemistry · doi:10.1021/jm0306430 · Cited by 10,057 · see citing works
Pérez-Riverol, Y., Csordas, A., Bai, J.-W., Bernal-Llinares, M., Hewapathirana, S., Kundu, D. J., Inuganti, A., Griss, J., Mayer, G., Eisenacher, M., et al. (2018) · Nucleic Acids Res. · doi:10.1093/nar/gky1106 · Cited by 6,216 · see citing works
A statistical model for identifying proteins by tandem mass spectrometry.
Nesvizhskii, A., Keller, A., Kolker, E., & Aebersold, R. (2003) · Analytical Chemistry · doi:10.1021/ac0341261 · Cited by 4,902 · see citing works
MDAnalysis: A toolkit for the analysis of molecular dynamics simulations
Michaud‐Agrawal, N., Denning, E. J., Woolf, T. B., & Beckstein, O. (2011) · Journal of Computational Chemistry · doi:10.1002/jcc.21787 · Cited by 4,549 · see citing works
Best, R. B., Zhu, X., Shim, J., Lopes, P. E. M., Mittal, J., Feig, M., & MacKerell, A. D. (2012) · Journal of Chemical Theory and Computation · doi:10.1021/ct300400x · Cited by 4,472 · see citing works
Update of the CHARMM all-atom additive force field for lipids: Validation on six lipid types
Klauda, J. B., Venable, R., Freites, J. A., O'Connor, J. W., Tobias, D., Mondragon-Ramirez, C., Vorobyov, I., MacKerell, A. D., & Pastor, R. (2010) · Journal of Physical Chemistry B · doi:10.1021/jp101759q · Cited by 4,369 · see citing works
CHARMM-GUI Membrane Builder Toward Realistic Biological Membrane Simulations
Wu, E., Cheng, X., Jo, S., Rui, H., Song, K., Dávila-Contreras, E. M., Qi, Y., Lee, J.-M., Monje-Galvan, V., Venable, R., et al. (2014) · Journal of Computational Chemistry · doi:10.1002/jcc.23702 · Cited by 2,563 · see citing works
MDAnalysis: A Python Package for the Rapid Analysis of Molecular Dynamics Simulations
Gowers, R. J., Linke, M., Barnoud, J., Reddy, T. J., Melo, M. N., Seyler, S. L., Domański, J., Dotson, D., Buchoux, S., Kenney, I. M., et al. (2016) · Proceedings of the Python in Science Conferences · doi:10.25080/majora-629e541a-00e · Cited by 2,085 · see citing works
Structure and Mechanism of the Lactose Permease of Escherichia coli
Abramson, J., Smirnova, I., Kasho, V. N., Verner, G., Kaback, H. R., & Iwata, S. (2003) · Science · doi:10.1126/science.1088196 · Cited by 1,389 · see citing works
Improved prediction of protein side‐chain conformations with SCWRL4
Krivov, G. G., Shapovalov, M. V., & Dunbrack, R. L. (2009) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.22488 · Cited by 1,312 · see citing works
Simple Allosteric Model for Membrane Pumps
Jardetzky, O. (1966) · Nature · doi:10.1038/211969a0 · Cited by 1,293 · see citing works
Peterson, A. C., Russell, J. D., Bailey, D. J., Westphall, M. S., & Coon, J. J. (2012) · Molecular & Cellular Proteomics · doi:10.1074/mcp.o112.020131 · Cited by 1,288 · see citing works
Gene splicing and mutagenesis by PCR-driven overlap extension
Heckman, K. L., & Pease, L. R. (2007) · Nature Protocols · doi:10.1038/nprot.2007.132 · Cited by 1,150 · see citing works
Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid
Nguyen, L. N., Ma, D., Shui, G., Wong, P., Cazenave-Gassiot, A., Zhang, X., Wenk, M. R., Goh, E. L. K., & Silver, D. L. (2014) · Nature · doi:10.1038/nature13241 · Cited by 1,048 · see citing works
Mfsd2a is critical for the formation and function of the blood-brain barrier
Ben-Zvi, A., Lacoste, B., Kur, E., Andreone, B. J., Mayshar, Y., Yan, H., & Gu, C. (2014) · Nature · doi:10.1038/nature13324 · Cited by 1,037 · see citing works
Structure and Mechanism of the Glycerol-3-Phosphate Transporter from Escherichia coli
Huang, Y., Lemieux, M. J., Song, J., Auer, M., & Wang, D. (2003) · Science · doi:10.1126/science.1087619 · Cited by 1,015 · see citing works
Crystal structure of the human glucose transporter GLUT1
Deng, D., Xu, C., Sun, P., Wu, J., Yan, C., Hu, M., & Yan, N. (2014) · Nature · doi:10.1038/nature13306 · Cited by 777 · see citing works
Sakr, A., Brégeon, F., Mège, J., Rolain, J., & Blin, O. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.02419 · Cited by 566 · see citing works
Ins and Outs of Major Facilitator Superfamily Antiporters
Law, C. J., Maloney, P. C., & Wang, D. (2008) · Annual Review of Microbiology · doi:10.1146/annurev.micro.61.080706.093329 · Cited by 512 · see citing works
Lipoteichoic Acid Synthesis and Function in Gram-Positive Bacteria
Percy, M. G., & Gründling, A. (2014) · Annual Review of Microbiology · doi:10.1146/annurev-micro-091213-112949 · Cited by 497 · see citing works
The major facilitator superfamily (MFS) revisited
Reddy, V. S., Shlykov, M. A., Castillo, R., Sun, E. I., & Saier, M. H. (2012) · FEBS Journal · doi:10.1111/j.1742-4658.2012.08588.x · Cited by 476 · see citing works
Crystal structure of a bacterial homologue of glucose transporters GLUT1–4
Sun, L., Zeng, X. W., Yan, C., Sun, X., Gong, X., Rao, Y., & Yan, N. (2012) · Nature · doi:10.1038/nature11524 · Cited by 472 · see citing works
Structures and General Transport Mechanisms by the Major Facilitator Superfamily (MFS)
Drew, D., North, R. A., Nagarathinam, K., & Tanabe, M. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.0c00983 · Cited by 471 · see citing works
Molecular structure of human P-glycoprotein in the ATP-bound, outward-facing conformation
Kim, Y., & Chen, J. (2018) · Science · doi:10.1126/science.aar7389 · Cited by 456 · see citing works
Understanding transport by the major facilitator superfamily (MFS): structures pave the way
Quistgaard, E. M., Löw, C., Guettou, F., & Nordlund, P. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2015.25 · Cited by 451 · see citing works
X-ray structure of a calcium-activated TMEM16 lipid scramblase
Brunner, J. D., Lim, N. K., Schenck, S., Duerst, A., & Dutzler, R. (2014) · Nature · doi:10.1038/nature13984 · Cited by 437 · see citing works
The Sphingolipid Transporter Spns2 Functions in Migration of Zebrafish Myocardial Precursors
Kawahara, A., Nishi, T., Hisano, Y., Fukui, H., Yamaguchi, A., & Mochizuki, N. (2008) · Science · doi:10.1126/science.1167449 · Cited by 405 · see citing works
Molecular basis of ligand recognition and transport by glucose transporters
Deng, D., Sun, P., Yan, C., Ke, M., Jiang, X. J., Xiong, L., Ren, W., Hirata, K., Yamamoto, M., Fan, S., et al. (2015) · Nature · doi:10.1038/nature14655 · Cited by 386 · see citing works
Structure of hepcidin-bound ferroportin reveals iron homeostatic mechanisms
Billesbølle, C. B., Azumaya, C. M., Kretsch, R. C., Powers, A. S., Gonen, S., Schneider, S., Arvedson, T., Dror, R. O., Cheng, Y., & Manglik, A. (2020) · Nature · doi:10.1038/s41586-020-2668-z · Cited by 344 · see citing works
Lipid flippases and their biological functions
Pomorski, T. G., & Menon, A. K. (2006) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-006-6167-7 · Cited by 336 · see citing works
The wall teichoic acid and lipoteichoic acid polymers of Staphylococcus aureus
Xia, G., Kohler, T. P., & Peschel, A. (2009) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2009.10.001 · Cited by 279 · see citing works
Commensal Staphylococci Influence Staphylococcus aureus Skin Colonization and Disease
Parlet, C. P., Severn, M. M., & Horswill, A. R. (2019) · Trends in Microbiology · doi:10.1016/j.tim.2019.01.008 · Cited by 275 · see citing works
Structural basis of MsbA-mediated lipopolysaccharide transport
Mi, W., Li, Y., Yoon, S. H., Ernst, R. K., Walz, T., & Liao, M. (2017) · Nature · doi:10.1038/nature23649 · Cited by 260 · see citing works
Complete Bypass of Restriction Systems for Major Staphylococcus aureus Lineages
Monk, I. R., Tree, J. J., Howden, B. P., Stinear, T. P., & Foster, T. J. (2015) · mBio · doi:10.1128/mbio.00308-15 · Cited by 242 · see citing works
Mfsd2b is essential for the sphingosine-1-phosphate export in erythrocytes and platelets
Vu, M. T., Ishizu, A.-N., Foo, J. C., Toh, X. R., Zhang, F., Whee, D. M., Torta, F. T., Cazenave‐Gassiot, A., Matsumura, T., Kim, S., et al. (2017) · Nature · doi:10.1038/nature24053 · Cited by 241 · see citing works
Structure and mechanism of the mammalian fructose transporter GLUT5
Nomura, N., Verdon, G., Kang, H. J., Shimamura, T., Nomura, Y., Sonoda, Y., Hussien, S. A., Qureshi, A. A., Coincon, M., Sato, Y., et al. (2015) · Nature · doi:10.1038/nature14909 · Cited by 240 · see citing works
Structure and mechanism of an active lipid-linked oligosaccharide flippase
Pérez, C., Gerber, S., Boilevin, J., Bucher, M., Darbre, T., Aebi, M., Reymond, J., & Locher, K. P. (2015) · Nature · doi:10.1038/nature14953 · Cited by 209 · see citing works
The Alternating-Access Mechanism of MFS Transporters Arises from Inverted-Topology Repeats
Radestock, S., & Forrest, L. R. (2011) · Journal of Molecular Biology · doi:10.1016/j.jmb.2011.02.008 · Cited by 202 · see citing works
Genes Required for Glycolipid Synthesis and Lipoteichoic Acid Anchoring in Staphylococcus aureus
Gründling, A., & Schneewind, O. (2007) · Journal of Bacteriology · doi:10.1128/jb.01683-06 · Cited by 199 · see citing works
Cryo-EM structures capture the transport cycle of the P4-ATPase flippase
Hiraizumi, M., Yamashita, K., Nishizawa, T., & Nureki, O. (2019) · Science · doi:10.1126/science.aay3353 · Cited by 185 · see citing works
Structure and autoregulation of a P4-ATPase lipid flippase
Timcenko, M., Lyons, J. A., Januliene, D., Ulstrup, J. J., Dieudonné, T., Montigny, C., Ash, M.-R., Karlsen, J. L., Boesen, T. P., Kühlbrandt, W., et al. (2019) · Nature · doi:10.1038/s41586-019-1344-7 · Cited by 178 · see citing works
Substrate-bound structure of the E. coli multidrug resistance transporter MdfA
Heng, J., Zhao, Y., Liu, M., Liu, Y., Fan, J., 王, X. 贤. W., Zhao, Y., & Zhang, X. C. (2015) · Cell Research · doi:10.1038/cr.2015.94 · Cited by 168 · see citing works
Ahrné, E., Glatter, T., Viganó, C., von Schubert, C., Nigg, E. A., & Schmidt, A. (2016) · Journal of Proteome Research · doi:10.1021/acs.jproteome.6b00066 · Cited by 165 · see citing works
Self-citationLipid somersaults: Uncovering the mechanisms of protein-mediated lipid flipping
Pomorski, T. G., & Menon, A. K. (2016) · Progress in Lipid Research · doi:10.1016/j.plipres.2016.08.003 · Cited by 165 · see citing works
Opsin Is a Phospholipid Flippase
Menon, I. A., Huber, T., Sanyal, S., Banerjee, S., Barré, P., Canis, S., Warren, J. D., Hwa, J., Sakmar, T. P., & Menon, A. K. (2011) · Current Biology · doi:10.1016/j.cub.2010.12.031 · Cited by 159 · see citing works
Diverse relations between ABC transporters and lipids: An overview
Neumann, J., Rose-Sperling, D., & Hellmich, U. A. (2016) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2016.09.023 · Cited by 150 · see citing works
Jorasch, P., Wolter, F. P., Zähringer, U., & Heinz, E. (1998) · Molecular Microbiology · doi:10.1046/j.1365-2958.1998.00930.x · Cited by 142 · see citing works
Koch, H.-G., Renate, H. A. A. S., & Fischer, W. (1984) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1984.tb07923.x · Cited by 130 · see citing works
Kiriukhin, M. Y., Debabov, D. V., Shinabarger, D. L., & Neuhaus, F. C. (2001) · Journal of Bacteriology · doi:10.1128/jb.183.11.3506-3514.2001 · Cited by 121 · see citing works
Structural basis of ω−3 fatty acid transport across the blood-brain barrier
Cater, R., Chua, G., Erramilli, S., Keener, J., Choy, B., Tokarz, P., Chin, C., Quek, D., Kloss, B., Pepe, J., et al. (2021) · Nature · doi:10.1038/s41586-021-03650-9 · Cited by 114 · see citing works
Structure and mechanism of blood–brain-barrier lipid transporter MFSD2A
Wood, C. A. P., Zhang, J., Aydın, D., Xu, Y., Andreone, B. J., Langen, U. H., Dror, R. O., Gu, C., & Feng, L. (2021) · Nature · doi:10.1038/s41586-021-03782-y · Cited by 106 · see citing works
Architecture of a channel-forming O-antigen polysaccharide ABC transporter
Bi, Y., Mann, E., Whitfield, C., & Zimmer, J. (2018) · Nature · doi:10.1038/nature25190 · Cited by 94 · see citing works
Lipoteichoic Acid Inhibits Staphylococcus aureus Biofilm Formation
Ahn, K. B., Baik, J. E., Yun, C., & Han, S. H. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.00327 · Cited by 85 · see citing works
Quek, D. Q. Y., Nguyen, L. N., Fan, H., & Silver, D. L. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.721035 · Cited by 81 · see citing works
Structural basis of ion transport and inhibition in ferroportin
Pan, Y., Ren, Z., Gao, S., Shen, J., Wang, L., Xu, Z., Yu, Y., Bachina, P., Zhang, H., Fan, X., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19458-6 · Cited by 81 · see citing works
The molecular basis for sugar import in malaria parasites
Qureshi, A. A., Suades, A., Matsuoka, R., Brock, J., McComas, S. E., Nji, E., Orellana, L., Claesson, M., Delemotte, L., & Drew, D. (2020) · Nature · doi:10.1038/s41586-020-1963-z · Cited by 77 · see citing works
Structure of the human lipid exporter ABCB4 in a lipid environment
Olsen, J. A., Alam, A., Kowal, J., Stieger, B., & Locher, K. P. (2019) · Nature Structural & Molecular Biology · doi:10.1038/s41594-019-0354-3 · Cited by 75 · see citing works
Fischer, W., Koch, H.-G., Rösel, P., Fiedler, F., & Schmuck, L. (1980) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)85528-x · Cited by 75 · see citing works
Angers, M., Uldry, M., Kong, D., Gimble, J. M., & Jetten, A. M. (2008) · Biochemical Journal · doi:10.1042/bj20080165 · Cited by 74 · see citing works
Conformational changes required for H+/Cl− exchange mediated by a CLC transporter
Basilio, D., Noack, K., Picollo, A., & Accardi, A. (2014) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2814 · Cited by 72 · see citing works
An embedded lipid in the multidrug transporter LmrP suggests a mechanism for polyspecificity
Debruycker, V., Hutchin, A., Masureel, M., Ficici, E., Martens, C., Legrand, P., Stein, R. A., Mchaourab, H. S., Faraldo-Gómez, J. D., Remaut, H., et al. (2020) · Nature Structural & Molecular Biology · doi:10.1038/s41594-020-0464-y · Cited by 69 · see citing works
Wang, S. C., Davejan, P. M., Hendargo, K. J., Javadi-Razaz, I., Chou, A., Yee, D. C., Ghazi, F., Lam, K. J. K., Conn, A. M., Madrigal, A. A., et al. (2020) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2020.183277 · Cited by 69 · see citing works
Harvat, E. M., Zhang, Y., Tran, C. V., Zhang, Z., Frank, M. W., Rock, C. O., & Saier, M. H. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m414368200 · Cited by 63 · see citing works
Hesser, A. R., Matano, L. M., Vickery, C. R., Wood, B. M., Santiago, A. G., Morris, H. G., Do, T., Losick, R. M., & Walker, S. (2020) · Journal of Bacteriology · doi:10.1128/jb.00149-20 · Cited by 57 · see citing works
Structure of a proton-dependent lipid transporter involved in lipoteichoic acids biosynthesis
Zhang, B., Liu, X., Lambert, E., Mas, G., Hiller, S., Veening, J., & Pérez, C. (2020) · Nature Structural & Molecular Biology · doi:10.1038/s41594-020-0425-5 · Cited by 41 · see citing works
Self-citationStructural Basis of Substrate-Independent Phosphorylation in a P4-ATPase Lipid Flippase
Timcenko, M., Dieudonné, T., Montigny, C., Boesen, T. P., Lyons, J. A., Lenoir, G., & Nissen, P. (2021) · Journal of Molecular Biology · doi:10.1016/j.jmb.2021.167062 · Cited by 40 · see citing works
Pérez, C., Mehdipour, A. R., Hummer, G., & Locher, K. P. (2019) · Structure · doi:10.1016/j.str.2019.01.013 · Cited by 35 · see citing works
Self-citationBiological function of SPNS2: From zebrafish to human
Zhu, X., Ren, K., Zeng, Y.-Z., Zheng, Z., & Yi, G. (2018) · Molecular Immunology · doi:10.1016/j.molimm.2018.08.025 · Cited by 25 · see citing works
X-Ray Structure of a Calcium Activated TMEM16 Lipid Scramblase
Brunner, J. D., Lim, N. K., & Schenck, S. (2015) · Biophysical Journal · doi:10.1016/j.bpj.2014.11.1881 · Cited by 21 · see citing works
Lin, Y., Deepak, R. N. V. K., Zheng, J. Z., Fan, H., & Zheng, L. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.005548 · Cited by 19 · see citing works
Stabilization and Crystallization of a Membrane Protein Involved in Lipid Transport
Zhang, B., & Pérez, C. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-0373-4_19 · Cited by 5 · see citing works
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2 of the 83 references couldn’t be matched to a known paper.
Cited by
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CHARMM-GUI Membrane Builder : Past, Current, and Future Developments and Applications
Feng, S., Park, S., Choi, Y. K., & Im, W. (2023) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.2c01246 · Cited by 193 · see citing works
Mfsd2a utilizes a flippase mechanism to mediate omega-3 fatty acid lysolipid transport
Chua, G. L., Tan, B. C., Loke, R. Y. J., He, M., Chin, C. F., Wong, B. H., Kuk, A. C. Y., Ding, M., Wenk, M. R., Guan, L., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2215290120 · Cited by 42 · see citing works
Substrate binding-induced conformational transitions in the omega-3 fatty acid transporter MFSD2A
Bergman, S., Cater, R. J., Plante, A., Mancia, F., & Khelashvili, G. (2023) · Nature Communications · doi:10.1038/s41467-023-39088-y · Cited by 24 · see citing works
Molecular mechanisms of Na+-driven bile acid transport in human NTCP
Lu, X., & Huang, J. (2024) · Biophysical Journal · doi:10.1016/j.bpj.2024.03.033 · Cited by 20 · see citing works
Dissecting the conformational complexity and mechanism of a bacterial heme transporter
Wu, D., Mehdipour, A. R., Finke, F., Goojani, H. G., Groh, R. R., Grund, T. N., Reichhart, T. M. B., Zimmermann, R., Welsch, S., Bald, D., et al. (2023) · Nature Chemical Biology · doi:10.1038/s41589-023-01314-5 · Cited by 22 · see citing works
Self-citationWang, S., Wang, K., Song, K., Lai, Z. W., Li, P., Li, D., Sun, Y., Mei, Y., Xu, C., & Liao, M. (2024) · Nature Communications · doi:10.1038/s41467-024-51948-9 · Cited by 18 · see citing works
Gonda, I., Sorrentino, S., Galazzo, L., Lichti, N. P., Arnold, F. M., Mehdipour, A. R., Bordignon, E., & Seeger, M. A. (2025) · Nature Communications · doi:10.1038/s41467-024-55136-7 · Cited by 16 · see citing works
Self-citationThe function of CozE proteins is linked to lipoteichoic acid biosynthesis in Staphylococcus aureus
Barbuti, M. D., Lambert, E., Myrbråten, I. S., Ducret, A., Stamsås, G. A., Wilhelm, L., Liu, X., Salehian, Z., Veening, J., Straume, D., et al. (2024) · mBio · doi:10.1128/mbio.01157-24 · Cited by 11 · see citing works
Self-citationMFSD2A in Focus: the Molecular Mechanism of Omega-3 Fatty Acid Transport
Blades, F., Yazici, A. T., Cater, R. J., & Mancia, F. (2025) · Physiology · doi:10.1152/physiol.00068.2024 · Cited by 11 · see citing works
An erythrocyte-centric view on the MFSD2B sphingosine-1-phosphate transporter
Ghaderi, S., & Levkau, B. (2023) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2023.108483 · Cited by 10 · see citing works
Fatty acid transporter MFSD2A is a multifunctional gatekeeper in brain and placenta
Walter, J. D., Remm, S., & Seeger, M. A. (2022) · Nature Structural & Molecular Biology · doi:10.1038/s41594-022-00788-6 · Cited by 8 · see citing works
Peripheral positions encode transport specificity in the small multidrug resistance exporters
Burata, O. E., O’Donnell, E., Hyun, J., Lucero, R. M., Thomas, J. E., Gibbs, E. M., Reacher, I., Carney, N., & Stockbridge, R. B. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2403273121 · Cited by 6 · see citing works
Li, D., Zhang, X., Yao, Y., Sun, X. J., Sun, J., Ma, X., Yuan, K., Bai, G., Pang, X., Hua, R., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2412653121 · Cited by 4 · see citing works
Complexation of CcmB with CcmACD safeguards heme translocation for cytochrome c maturation
Xu, Y., Wang, W., Zhang, Q., Han, S., Wang, J., Wu, S., & Gao, H. (2025) · mLife · doi:10.1002/mlf2.12150 · Cited by 3 · see citing works
SPIN-4/Spinster supports sperm activation in C. elegans via sphingosine-1-phosphate transport
Flora, Y., & Bohnert, K. A. (2023) · Developmental Biology · doi:10.1016/j.ydbio.2023.09.013 · Cited by 1 · see citing works
Guan, M., Xie, C., Xue, Y., Lu, J., Jiang, Q., Yin, M., Yan, S., & Shen, J. (2026) · Plant Biotechnology Journal · doi:10.1111/pbi.70689 · Cited by 1 · see citing works
Burata, O. E., O’Donnell, E., Hyun, J., Lucero, R. M., Thomas, J. E., Gibbs, E. M., Reacher, I., Carney, N., & Stockbridge, R. B. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.02.06.579181 · Cited by 1 · see citing works
LetA defines a structurally distinct transporter family involved in lipid traffickingPreprint
Santarossa, C., Li, Y., Yousef, S., Hasdemir, H. S., Rodriguez, C. C., Haase, M. B., Baek, M., Coudray, N., Pavek, J. G., Focke, K. N., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.03.21.644421 · Cited by 1 · see citing works
How to measure omega-3 fatty acid lysolipid flipping: The ultimate guide
Pérez, C. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2302321120
Mechanism of Phosphatidylserine Lipid Scrambling by Human SERINC3, an HIV-1 Restriction FactorPreprint
Banerjee, P., Yeager, M. J., & Voth, G. A. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.11.13.688349
Analysis of glycosyldiacylglycerols produced by the zoonotic pathogen Streptococcus suis
Gauda, W., Hsu, F., Schombel, U., Thomsen, S., Fittipaldi, N., Gottschalk, M. G., Schwudke, D., & Gisch, N. (2026) · Chemistry and Physics of Lipids · doi:10.1016/j.chemphyslip.2026.105602
Paige, T. J., Chen, J., Roy, A. L., Sampson, C. D. D., Cooper, B. F., Batson, M., Scarsbrook, H. L., Forrest, L. R., Isom, G. L., Mas, C., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.09.20.752871
- Authors
- Lambert, E., Mehdipour, A. R., Schmidt, A., Hummer, G., & Perez, C.
- Affiliations
- University of Basel (CH)
- Ghent University (BE)
- Goethe University Frankfurt (DE)
- Venue
- Nature Communications
- Published
- 2022-02-23
- Volume
- 13
- Issue
- 1
- Pages
- 1022-1022
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC8866510
- OpenAlex
- W4220660898
- Cited by
- 24
- References
- 83
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 6 · 2023: 8 · 2022: 1
- FWCI
- 2.20
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- edoc (University of Basel) (acceptedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) (submittedVersion, cc-by)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (PP00P3_198903)
- Deutsche Forschungsgemeinschaft (SFB 807)
- Max-Planck-Gesellschaft
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- major facilitator superfamily, lipid transfer proteins, Staphylococcus aureus, substrate specificity, lipid translocation
- MeSH terms
- Biological Transport, Lipids, Protein Conformation, Protons, Membrane Transport Proteins, Molecular Dynamics Simulation
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