Crystal structure of the human lysosomal mTORC1 scaffold complex and its impact on signaling
Abstract
Structure of human mTORC1 components: The mTORC1 (mechanistic target of rapamycin complex 1) complex garners much attention as a signaling hub that coordinates input from growth-factor receptors and nutrient availability with metabolism and cell growth and proliferation. de Araujo et al. report the crystal structure of the LAMTOR (or “Ragulator”) complex that helps assemble mTORC1 at the lysosomal membrane for activation. The structure and functional studies reveal how LAMTOR1 wraps around the other subunits to hold them in place and interacts with the Rag guanosine triphosphatases in the complex. Science , this issue p. 377
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The heptameric Ragulator-Rag complex structure showed Rag C-terminal roadblock domains binding to the LAMTOR2-LAMTOR3 heterodimer, building a tower of three roadblock domain-mediated heterodimers tied together by the extended LAMTOR1 subunit, and presenting the GTPase domains for interaction with RAPTOR.
“The heptameric Ragulator-Rag complex structure showed Rag C-terminal roadblock domains binding to the LAMTOR2-LAMTOR3 heterodimer (de Araujo et al., 2017; Su et al., 2017; Yonehara et al., 2017) (Fig. 4B), thus building a tower of three roadblock domain-mediated heterodimers tied together by the extended LAMTOR1 subunit, and presenting the GTPase domains for interaction with RAPTOR.”
From Signal integration in the (m)TORC1 growth pathway (2018) · cites this paper as de Araujo et al., 2017
When the Rag heterodimer binds Ragulator, the N-terminal portion of LAMTOR1 encompassing residues 47-64 is resolved, forming an α-helix which packs against the RagC roadblock domain, whereas in the Ragulator complex alone this region of LAMTOR1 was disordered.
“It is important to note that when the Rag heterodimer binds Ragulator, the N-terminal portion of LAMTOR1 encompassing residues 47-64 is resolved, forming an α-helix which packs against the RagC roadblock domain, whereas in the Ragulator complex alone this region of LAMTOR1 was disordered (de Araujo et al., 2017; Yonehara et al., 2017).”
From Signal integration in the (m)TORC1 growth pathway (2018) · cites this paper as de Araujo et al., 2017
Cites
Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
LAEMMLI, U. K. (1970) · Nature · doi:10.1038/227680a0 · Cited by 249,961 · see citing works
Features and development of Coot
Emsley, P., Lohkamp, B., Scott, W. G., & Cowtan, K. D. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910007493 · Cited by 27,510 · see citing works
<i>PHENIX</i> : a comprehensive Python-based system for macromolecular structure solution
Adams, P. D., Afonine, P. V., Bunkóczi, G., Chen, V. B., Davis, I. W., Echols, N., Headd, J. J., Hung, L.-W., Kapral, G. J., Grosse-Kunstleve, R. W., et al. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909052925 · Cited by 23,716 · see citing works
<i>Phaser</i> crystallographic software
McCoy, A. J., Grosse-Kunstleve, R. W., Adams, P. D., Winn, M. D., Storoni, L. C., & Read, R. J. (2007) · Journal of Applied Crystallography · doi:10.1107/s0021889807021206 · Cited by 20,612 · see citing works
Kabsch, W. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909047337 · Cited by 16,463 · see citing works
Refinement of Macromolecular Structures by the Maximum-Likelihood Method
Murshudov, G. N., Vagin, A. A., & Dodson, E. J. (1997) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444996012255 · Cited by 14,671 · 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
Inference of macromolecular assemblies from crystalline state.
Krissinel, E., & Henrick, K. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.05.022 · Cited by 10,189 · see citing works
Universal sample preparation method for proteome analysis
Wiśniewski, J. R., Zougman, A., Nagaraj, N., & Mann, M. (2009) · Nature Methods · doi:10.1038/nmeth.1322 · Cited by 8,352 · see citing works
Towards automated crystallographic structure refinement with <i>phenix.refine</i>
Afonine, P. V., Grosse-Kunstleve, R. W., Echols, N., Headd, J. J., Moriarty, N. W., Mustyakimov, M., Terwilliger, T. C., Urzhumtsev, A., Zwart, P. H., & Adams, P. D. (2012) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444912001308 · Cited by 5,511 · see citing works
Improved vectors and genome-wide libraries for CRISPR screening
Sanjana, N. E., Shalem, O., & Zhang, F. (2014) · Nature Methods · doi:10.1038/nmeth.3047 · Cited by 5,239 · see citing works
Genome-scale CRISPR-Cas9 knockout screening in human cells
Shalem, O., Sanjana, N. E., Hartenian, E., Shi, X., Scott, D. A., Mikkelsen, T. S., Heckl, D., Ebert, B. L., Root, D. E., Doench, J. G., et al. (2014) · Science · doi:10.1126/science.1247005 · Cited by 5,234 · see citing works
MOLREP : an Automated Program for Molecular Replacement
Vagin, A. A., & Teplyakov, A. (1997) · Journal of Applied Crystallography · doi:10.1107/s0021889897006766 · Cited by 4,791 · see citing works
DNA targeting specificity of RNA-guided Cas9 nucleases
Hsu, P. D., Scott, D. A., Weinstein, J. A., Ran, F. A., Konermann, S., Agarwala, V., Li, Y., Fine, E. J., Wu, X., Shalem, O., et al. (2013) · Nature Biotechnology · doi:10.1038/nbt.2647 · Cited by 4,741 · see citing works
Assay of proteins in the presence of interfering materials
Bensadoun, A., & Weinstein, D. (1976) · Analytical Biochemistry · doi:10.1016/s0003-2697(76)80064-4 · Cited by 3,191 · see citing works
The Rag GTPases Bind Raptor and Mediate Amino Acid Signaling to mTORC1
Sancak, Y., Peterson, T. R., Shaul, Y. D., Lindquist, R. A., Thoreen, C. C., Bar-Peled, L., & Sabatini, D. M. (2008) · Science · doi:10.1126/science.1157535 · Cited by 2,773 · see citing works
Sancak, Y., Bar-Peled, L., Zoncu, R., Markhard, A. L., Nada, S., & Sabatini, D. M. (2010) · Cell · doi:10.1016/j.cell.2010.02.024 · Cited by 2,464 · see citing works
The Buccaneer software for automated model building. 1. Tracing protein chains
Cowtan, K. D. (2006) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444906022116 · Cited by 1,834 · see citing works
Identification and characterization of essential genes in the human genome
Wang, T., Birsoy, K., Hughes, N. W., Krupczak, K. M., Post, Y., Wei, J. J., Lander, E. S., & Sabatini, D. M. (2015) · Science · doi:10.1126/science.aac7041 · Cited by 1,617 · see citing works
Automated macromolecular model building for X-ray crystallography using ARP/wARP version 7
Langer, G., Cohen, S. X., Lamzin, V. S., & Perrakis, A. (2008) · Nature Protocols · doi:10.1038/nprot.2008.91 · Cited by 1,606 · see citing works
Ragulator Is a GEF for the Rag GTPases that Signal Amino Acid Levels to mTORC1
Bar-Peled, L., Schweitzer, L. D., Zoncu, R., & Sabatini, D. M. (2012) · Cell · doi:10.1016/j.cell.2012.07.032 · Cited by 918 · see citing works
Gene essentiality and synthetic lethality in haploid human cells
Blomen, V. A., Májek, P., Jae, L. T., Bigenzahn, J. W., Nieuwenhuis, J., Staring, J., Sacco, R., van Diemen, F. R., Olk, N., Stukalov, A., et al. (2015) · Science · doi:10.1126/science.aac7557 · Cited by 857 · see citing works
Regulation of mTORC1 by amino acids
Bar-Peled, L., & Sabatini, D. M. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.03.003 · Cited by 773 · see citing works
Wang, S., Tsun, Z., Wolfson, R. L., Shen, K., Wyant, G., Plovanich, M. E., Yuan, E. D., Jones, T. D., Chantranupong, L., Comb, W. C., et al. (2015) · Science · doi:10.1126/science.1257132 · Cited by 772 · see citing works
SLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1
Rebsamen, M., Pochini, L., Stasyk, T., de Araújo, M. E. G., Galluccio, M., Kandasamy, R. K., Snijder, B., Fauster, A., Rudashevskaya, E. L., Bruckner, M., et al. (2015) · Nature · doi:10.1038/nature14107 · Cited by 673 · see citing works
Self-citationControlled expression of transgenes introduced by in vivo electroporation
Matsuda, T., & Cepko, C. L. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610155104 · Cited by 666 · see citing works
CHAINSAW: a program for mutating pdb files used as templates in molecular replacement
Stein, N. (2008) · Journal of Applied Crystallography · doi:10.1107/s0021889808006985 · Cited by 536 · see citing works
The dawn of the age of amino acid sensors for the mTORC1 pathway
Wolfson, R. L., & Sabatini, D. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.07.001 · Cited by 500 · see citing works
BORC, a Multisubunit Complex that Regulates Lysosome Positioning
Pu, J., Schindler, C., Jia, R., Jarník, M., Backlund, P. S., & Bonifacino, J. S. (2015) · Developmental Cell · doi:10.1016/j.devcel.2015.02.011 · Cited by 391 · see citing works
Teis, D., Wunderlich, W., & Huber, L. A. (2002) · Developmental Cell · doi:10.1016/s1534-5807(02)00364-7 · Cited by 371 · see citing works
Self-citationStavroX—A Software for Analyzing Crosslinked Products in Protein Interaction Studies
Götze, M., Pettelkau, J., Schaks, S., Bosse, K., Ihling, C. H., Krauth, F., Fritzsche, R., Kühn, U., & Sinz, A. (2011) · Journal of the American Society for Mass Spectrometry · doi:10.1007/s13361-011-0261-2 · Cited by 345 · see citing works
Nada, S., Hondo, A., Kasai, A., Koike, M., Saito, K., Uchiyama, Y., & Okada, M. (2009) · The EMBO Journal · doi:10.1038/emboj.2008.308 · Cited by 341 · see citing works
Amino Acid-Dependent mTORC1 Regulation by the Lysosomal Membrane Protein SLC38A9
Jung, J., Genau, H. M., & Behrends, C. (2015) · Molecular and Cellular Biology · doi:10.1128/mcb.00125-15 · Cited by 266 · see citing works
Cost, G. J., & Boeke, J. D. (1998) · Biochemistry · doi:10.1021/bi981858s · Cited by 242 · see citing works
Low-resolution refinement tools in REFMAC5
Nicholls, R. A., Long, F., & Murshudov, G. N. (2012) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s090744491105606x · Cited by 239 · see citing works
Gabadinho, J., Beteva, A., Guijarro, M., Rey‐Bakaikoa, V., Spruce, D., Bowler, M. W., Brockhauser, S., Flot, D. M., Gordon, E. J., Hall, D. R., et al. (2010) · Journal of Synchrotron Radiation · doi:10.1107/s0909049510020005 · Cited by 230 · see citing works
The Protein Interaction Landscape of the Human CMGC Kinase Group
Varjosalo, M. T., Keskitalo, S., van Drogen, A., Nurkkala, H., Vichalkovski, A., Aebersold, R. H., & Gstaiger, M. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.03.027 · Cited by 221 · see citing works
Teis, D., Taub, N., Kurzbauer, R., Hilber, D., de Araujo, M. E. G., Erlacher, M., Offterdinger, M., Villunger, A., Geley, S., Bohn, G., et al. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200607025 · Cited by 210 · see citing works
Self-citationImproved low-resolution crystallographic refinement with Phenix and Rosetta
DiMaio, F., Echols, N., Headd, J. J., Terwilliger, T. C., Adams, P. D., & Baker, D. A. (2013) · Nature Methods · doi:10.1038/nmeth.2648 · Cited by 179 · see citing works
Dynamics of mTORC1 activation in response to amino acids
Manifava, M., Smith, M., Rotondo, S., Walker, S. A., Niewczas, I., Zoncu, R., Clark, J., & Ktistakis, N. (2016) · eLife · doi:10.7554/elife.19960 · Cited by 108 · see citing works
A PCR Based Protocol for Detecting Indel Mutations Induced by TALENs and CRISPR/Cas9 in Zebrafish
Yu, C., Zhang, Y., Yao, S., & Wei, Y. (2014) · PLoS ONE · doi:10.1371/journal.pone.0098282 · Cited by 102 · see citing works
Vijayachandran, L. S., Viola, C., Garzoni, F., Trowitzsch, S., Bieniossek, C., Chaillet, M., Schaffitzel, C., Busso, D., Romier, C., Poterszman, A., et al. (2011) · Journal of Structural Biology · doi:10.1016/j.jsb.2011.03.007 · Cited by 99 · see citing works
Gong, R., Li, L., Liu, Y., Wang, P., Yang, H., Wang, L., Cheng, J., Guan, K.-L., & Xu, Y. (2011) · Genes & Development · doi:10.1101/gad.16968011 · Cited by 98 · see citing works
Schiefermeier-Mach, N., Scheffler, J. M., de Araújo, M. E. G., Stasyk, T., Yordanov, T. E., Ebner, H. L., Offterdinger, M., Munck, S., Hess, M. W., Wickström, S. A., et al. (2014) · The Journal of Cell Biology · doi:10.1083/jcb.201310043 · Cited by 95 · see citing works
Self-citationKurzbauer, R., Teis, D., de Araujo, M. E. G., Maurer-Stroh, S., Eisenhaber, F., Bourenkov, G. P., Bartunik, H. D., Hekman, M., Rapp, U. R., Huber, L. A., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0403435101 · Cited by 95 · see citing works
Self-citationPowis, K., Zhang, T., Panchaud, N., Wang, R., Virgilio, C. D., & Ding, J. (2015) · Cell Research · doi:10.1038/cr.2015.86 · Cited by 80 · see citing works
Dynamic relocation of the TORC1–Gtr1/2–Ego1/2/3 complex is regulated by Gtr1 and Gtr2
Kira, S., Kumano, Y., Ukai, H., Takeda, E., Matsuura, A., & Noda, T. (2016) · Molecular Biology of the Cell · doi:10.1091/mbc.e15-07-0470 · Cited by 71 · see citing works
Jeong, J.-H., Lee, K.-H., Kim, Y.-M., Kim, D.-H., Oh, B.-H., & Kim, Y.-G. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.c112.384420 · Cited by 68 · see citing works
The Structure of the MAPK Scaffold, MP1, Bound to Its Partner, p14
Lunin, V. V., Munger, C., Wagner, J., Ye, Z., Cygler, M., & Sacher, M. G. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m401648200 · Cited by 67 · see citing works
Zhang, T., Gulli, M., Yang, H., VIRGILIO, C. D., & Ding, J. (2012) · Structure · doi:10.1016/j.str.2012.09.019 · Cited by 63 · see citing works
LAMTOR2 regulates dendritic cell homeostasis through FLT3-dependent mTOR signalling
Scheffler, J. M., Sparber, F., Tripp, C. H., Herrmann, C., Humenberger, A., Blitz, J., Romani, N., Stoitzner, P., & Huber, L. A. (2014) · Nature Communications · doi:10.1038/ncomms6138 · Cited by 46 · see citing works
Self-citationThe late endosome/lysosome-anchored p18-mTORC1 pathway controls terminal maturation of lysosomes
Takahashi, Y., Nada, S., Mori, S., Soma‐Nagae, T., Oneyama, C., & Okada, M. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.12.082 · Cited by 44 · see citing works
Hall, J., Song, Y., Karplus, P. A., & Barbar, E. J. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.103861 · Cited by 41 · see citing works
Disruption of the Rag-Ragulator complex by c17orf59 inhibits mTORC1
Schweitzer, L. D., Comb, W. C., Bar-Peled, L., & Sabatini, D. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.07.052 · Cited by 38 · see citing works
Garcia-Saez, I., Lacroix, F., Blot, D., Gabel, F., & Skoufias, D. A. (2010) · Journal of Molecular Biology · doi:10.1016/j.jmb.2010.10.046 · Cited by 36 · see citing works
de Araújo, M. E. G., Stasyk, T., Taub, N., Ebner, H. L., Fürst, B., Filipek, P. A., Weys, S., Hess, M. W., Lindner, H. H., Kremser, L., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.349480 · Cited by 33 · see citing works
Self-citationThe MultiBac Protein Complex Production Platform at the EMBL
Berger, I., Garzoni, F., Chaillet, M., Haffke, M., Gupta, K., & Aubert, A. (2013) · Journal of Visualized Experiments · doi:10.3791/50159 · Cited by 30 · see citing works
Taub, N., Nairz, M., Hilber, D., Hess, M. W., Weiß, G., & Huber, L. A. (2012) · Journal of Cell Science · doi:10.1242/jcs.100073 · Cited by 28 · see citing works
Self-citationLAMTOR1 depletion induces p53-dependent apoptosis via aberrant lysosomal activation
Malek, M., Guillaumot, P., Huber, A.-L., Lebeau, J., Pétrilli, V., Kfoury, A., Mikaélian, I., Renno, T., & Manié, S. N. (2012) · Cell Death and Disease · doi:10.1038/cddis.2012.39 · Cited by 24 · see citing works
Interactions between Kinase Scaffold MP1/p14 and Its Endosomal Anchoring Protein p18
Magee, J., & Cygler, M. (2011) · Biochemistry · doi:10.1021/bi101972y · Cited by 23 · see citing works
The MultiBac Protein Complex Production Platform at the EMBL
Berger, I., Garzoni, F., Chaillet, M., Haffke, M., Gupta, K., & Aubert, A. (2013) · Journal of Visualized Experiments · doi:10.3791/50159-v · Cited by 12 · see citing works
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Condon, K. J., & Sabatini, D. (2019) · Journal of Cell Science · doi:10.1242/jcs.222570 · Cited by 288 · see citing works
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Takahara, T., Amemiya, Y., Sugiyama, R., Maki, M., & Shibata, H. (2020) · Journal of Biomedical Science · doi:10.1186/s12929-020-00679-2 · Cited by 300 · see citing works
Goul, C., Peruzzo, R., & Zoncu, R. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00641-8 · Cited by 269 · see citing works
Structural basis for the docking of mTORC1 on the lysosomal surface
Rogala, K. B., Gu, X., Kedir, J. F., Abu-Remaileh, M., Bianchi, L. F., Bottino, A. M. S., Dueholm, R., Niehaus, A., Overwijn, D., Fils, A.-C. P., et al. (2019) · Science · doi:10.1126/science.aay0166 · Cited by 191 · see citing works
Davis, O. B., Shin, H. R., Lim, C.-Y., Wu, E. Y., Kukurugya, M., Maher, C. F., Perera, R. M., Ordonez, M. P., & Zoncu, R. (2021) · Developmental Cell · doi:10.1016/j.devcel.2020.11.016 · Cited by 200 · see citing works
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Ou, X., Tan, Y., Xie, J., Yuan, J., Deng, X., Shao, R., Song, C., Cao, X., Xie, X., He, R., et al. (2024) · Drug Resistance Updates · doi:10.1016/j.drup.2024.101063 · Cited by 156 · see citing works
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Nowosad, A., Jeannot, P., Callot, C., Creff, J., Perchey, R. T., Joffre, C., Codogno, P., Manenti, S., & Besson, A. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0554-4 · Cited by 144 · see citing works
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Filipek, P. A., de Araujo, M. E. G., Vogel, G. F., De Smet, C. H., Eberharter, D., Rebsamen, M., Rudashevskaya, E. L., Kremser, L., Yordanov, T., Tschaikner, P., et al. (2017) · Journal of Cell Biology · doi:10.1083/jcb.201703061 · Cited by 119 · see citing works
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Lawrence, R., Cho, K., Rappold, R., Thrun, A., Tofaute, M., Kim, D. J., Moldavski, O., Hurley, J., & Zoncu, R. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0148-6 · Cited by 96 · see citing works
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Lee, M.-J., Kim, J. H., Yoon, I., Lee, C., Fallahi-Sichani, M., Kang, J., Kang, J., Guo, M., Lee, K.-Y., Han, G., et al. (2018) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1801287115 · Cited by 82 · see citing works
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Yonehara, R., Nada, S., Nakai, T., Nakai, M., Kitamura, A., Ogawa, A., Nakatsumi, H., Nakayama, K. I., Li, S., Standley, D. M., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01762-3 · Cited by 75 · see citing works
Structural mechanism for amino acid-dependent Rag GTPase nucleotide state switching by SLC38A9
Fromm, S. A., Lawrence, R. E., & Hurley, J. H. (2020) · Nature Structural & Molecular Biology · doi:10.1038/s41594-020-0490-9 · Cited by 72 · see citing works
Structural insight into the Ragulator complex which anchors mTORC1 to the lysosomal membrane
Mu, Z., Wang, L., Deng, W., Wang, J., & Wu, G. (2017) · Cell Discovery · doi:10.1038/celldisc.2017.49 · Cited by 63 · see citing works
Clinically Precedented Protein Kinases: Rationale for Their Use in Neurodegenerative Disease
Benn, C., & Dawson, L. A. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.00242 · Cited by 57 · see citing works
Sun, J., Liu, Y., Jia, Y., Tran, J., Hao, X., Lin, W., LYNCH, G. S., Baudry, M., & Bi, X. (2018) · eLife · doi:10.7554/elife.37993 · Cited by 57 · see citing works
SLC15A4 controls endolysosomal TLR7–9 responses by recruiting the innate immune adaptor TASL
Zhang, H., Bernaleau, L., Delacrétaz, M., Hasanovic, E., Drobek, A., Eibel, H., & Rebsamen, M. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112916 · Cited by 52 · see citing works
Egri, S., Ouch, C., Chou, H., Yu, Z.-H., Song, K.-K., Xu, C., & Shen, K. (2022) · Molecules and Cells · doi:10.1016/j.molcel.2022.03.002 · Cited by 43 · see citing works
Kahlhofer, J., & Teis, D. (2022) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.13821 · Cited by 48 · see citing works
Conserved and Divergent Mechanisms That Control TORC1 in Yeasts and Mammals
Morozumi, Y., & Shiozaki, K. (2021) · Genes · doi:10.3390/genes12010088 · Cited by 44 · see citing works
Yordanov, T. E., Hipolito, V. E. B., Liebscher, G., Vogel, G. F., Stasyk, T., Herrmann, C., Geley, S., Teis, D., Botelho, R. J., Hess, M. W., et al. (2019) · Traffic · doi:10.1111/tra.12679 · Cited by 46 · see citing works
Self-citationThe lysosomal Ragulator complex activates NLRP3 inflammasome in vivo via HDAC6
Tsujimoto, K., Jo, T., Nagira, D., Konaka, H., Park, J. H., Yoshimura, S., Ninomiya, A., Sugihara, F., Hirayama, T., Itotagawa, E., et al. (2022) · The EMBO Journal · doi:10.15252/embj.2022111389 · Cited by 45 · see citing works
Structural basis for mTORC1 activation on the lysosomal membrane
Cui, Z., Esposito, A., Napolitano, G., Ballabio, A., & Hurley, J. H. (2025) · Nature · doi:10.1038/s41586-025-09545-3 · Cited by 45 · see citing works
Chemoproteomic development of SLC15A4 inhibitors with anti-inflammatory activity
Chiu, T.-Y., Lazar, D. C., Wang, W., Wozniak, J. M., Jadhav, A. M., Li, W., Gazaniga, N. R., Theofilopoulos, A. N., Teijaro, J. R., & Parker, C. G. (2024) · Nature Chemical Biology · doi:10.1038/s41589-023-01527-8 · Cited by 43 · see citing works
Zhao, Y., Cholewa, J., Shang, H.-Y., Yang, Y.-Q., Ding, X., Wang, Q., Su, Q.-S., Zanchi, N. E., & Xia, Z. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.646482 · Cited by 41 · see citing works
The low-density lipoprotein receptor–mTORC1 axis coordinates CD8+ T cell activation
Bonacina, F., Moregola, A., Svecla, M., Coe, D., Uboldi, P., Fraire, S., Beretta, S., Beretta, G., Pellegatta, F., Catapano, A. L., et al. (2022) · The Journal of Cell Biology · doi:10.1083/jcb.202202011 · Cited by 40 · see citing works
Structural Insights into TOR Signaling
Tafur, L., Kefauver, J. M., & Loewith, R. (2020) · Genes · doi:10.3390/genes11080885 · Cited by 39 · see citing works
Sensors for the mTORC1 pathway regulated by amino acids
Li, X.-Z., & Yan, X. (2019) · Journal of Zhejiang University SCIENCE B · doi:10.1631/jzus.b1900181 · Cited by 38 · see citing works
Nutrient Signaling and Lysosome Positioning Crosstalk Through a Multifunctional Protein, Folliculin
Garrido, N. D. M., & Aylett, C. H. S. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00108 · Cited by 36 · see citing works
Brain-enriched RagB isoforms regulate the dynamics of mTORC1 activity through GATOR1 inhibition
Figlia, G., Müller, S., Hagenston, A. M., Kleber, S., Roiuk, M., Quast, J.-P., ten Bosch, N., Ibañez, D. C., Mauceri, D., Martin-Villalba, A., et al. (2022) · Nature Cell Biology · doi:10.1038/s41556-022-00977-x · Cited by 24 · see citing works
Organelle proteomic profiling reveals lysosomal heterogeneity in association with longevity
Yu, Y., Gao, S. M., Guan, Y., Hu, P.-W., Zhang, Q., Liu, J., Jing, B., Zhao, Q., Sabatini, D. M., Abu-Remaileh, M., et al. (2024) · eLife · doi:10.7554/elife.85214 · Cited by 37 · see citing works
A conformational change in the N terminus of SLC38A9 signals mTORC1 activation
Lei, H., Mu, X., Hattne, J., & Gonen, T. (2020) · Structure · doi:10.1016/j.str.2020.11.014 · Cited by 38 · see citing works
Structural mechanisms of the mTOR pathway
Linde-Garelli, K. Y., & Rogala, K. B. (2023) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2023.102663 · Cited by 37 · see citing works
The coding and non-coding transcriptional landscape of subependymal giant cell astrocytomas
Bongaarts, A., van Scheppingen, J., Korotkov, A., Mijnsbergen, C., Anink, J. J., Jansen, F. E., Spliet, W. G. M., den Dunnen, W. F. A., Gruber, V., Scholl, T. O., et al. (2019) · Brain · doi:10.1093/brain/awz370 · Cited by 37 · see citing works
Sun, J., Liu, Y., Hao, X., Lin, W., Su, W., Chiang, E., Baudry, M., & Bi, X. (2022) · The EMBO Journal · doi:10.15252/embj.2021108119 · Cited by 35 · see citing works
Cross-linking of the endolysosomal system reveals potential flotillin structures and cargo
Singh, J., Elhabashy, H., Muthukottiappan, P., Stepath, M., Eisenacher, M., Kohlbacher, O., Gieselmann, V., & Winter, D. (2022) · Nature Communications · doi:10.1038/s41467-022-33951-0 · Cited by 34 · see citing works
RORα is critical for mTORC1 activity in T cell-mediated colitis
Chi, X., Jin, W., Bai, X., Zhao, X., Shao, J., Li, J., Sun, Q., Su, B., Wang, X., Yang, X. O., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109682 · Cited by 33 · see citing works
AI-guided pipeline for protein–protein interaction drug discovery identifies a SARS-CoV-2 inhibitor
Trepte, P., Secker, C., Olivet, J., Blavier, J., Kostova, S., Maseko, S. B., Minia, I., Silva Ramos, E., Cassonnet, P., Golusik, S., et al. (2024) · Molecular Systems Biology · doi:10.1038/s44320-024-00019-8 · Cited by 35 · see citing works
Niu, F., Li, Z., Ren, Y., Li, Z., Guan, H., Li, Y., Zhang, Y., Li, Y., Yang, J., Lü, Q., et al. (2023) · Redox Biology · doi:10.1016/j.redox.2023.102824 · Cited by 28 · see citing works
LAMTOR1 decreased exosomal PD-L1 to enhance immunotherapy efficacy in non-small cell lung cancer
Wu, B., Huang, X., Shi, X., Jiang, M., Liu, H., & Zhao, L. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02099-4 · Cited by 28 · see citing works
mTORC1 Crosstalk With Stress Granules in Aging and Age-Related Diseases
Sandoval, M. C., Heberle, A. M., Rehbein, U., Barile, C., Pittol, J. M. R., & Thedieck, K. (2021) · Frontiers in Aging · doi:10.3389/fragi.2021.761333 · Cited by 27 · see citing works
Ragulator—a multifaceted regulator of lysosomal signaling and trafficking
Colaço, A., & Jäättelä, M. (2017) · The Journal of Cell Biology · doi:10.1083/jcb.201710039 · Cited by 28 · see citing works
Nakatani, T., Tsujimoto, K., Park, J., Jo, T., Kimura, T., Hayama, Y., Konaka, H., Morita, T., Kato, Y., Nishide, M., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23654-3 · Cited by 27 · see citing works
The TMEM127 human tumor suppressor is a component of the mTORC1 lysosomal nutrient-sensing complex
Deng, Y., Qin, Y., Srikantan, S., Luo, A., Cheng, Z.-M., Flores, S. K., Vogel, K. S., Wang, E., & Dahia, P. L. M. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddy095 · Cited by 25 · see citing works
Structure of the Mon1-Ccz1 complex reveals molecular basis of membrane binding for Rab7 activation
Klink, B. U., Herrmann, E., Antoni, C., Langemeyer, L., Kiontke, S., Gatsogiannis, C., Ungermann, C., Raunser, S., & Kümmel, D. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2121494119 · Cited by 26 · see citing works
Chen, Y., Leng, M., Gao, Y., Zhan, D., Choi, J. M., Song, L., Li, K., Xia, X., Zhang, C., Liu, M., et al. (2019) · Journal of Proteome Research · doi:10.1021/acs.jproteome.9b00427 · Cited by 25 · see citing works
Nanoparticles for inducing Gaucher disease-like damage in cancer cells
Yue, C., Lu, W., Fan, S., Huang, Z., Yang, J., Dong, H. Y., Zhang, X., Shang, Y., Lai, W., Li, D., et al. (2024) · Nature Nanotechnology · doi:10.1038/s41565-024-01668-4 · Cited by 23 · see citing works
Structural insights into the EGO-TC–mediated membrane tethering of the TORC1-regulatory Rag GTPases
Zhang, T., Gulli, M., Zhang, Z., Tang, X. H., Ye, J., VIRGILIO, C. D., & Ding, J. (2019) · Science Advances · doi:10.1126/sciadv.aax8164 · Cited by 22 · see citing works
The Ragulator complex: delving its multifunctional impact on metabolism and beyond
Tsujimoto, K., Takamatsu, H., & Kumanogoh, A. (2023) · Inflammation and Regeneration · doi:10.1186/s41232-023-00278-2 · Cited by 20 · see citing works
Mangione, M. C., Wen, J., & Cao, D. J. (2023) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2023.10.011 · Cited by 20 · see citing works
Tran, L. T., Akıl, C., Senju, Y., & Robinson, R. C. (2024) · Communications Biology · doi:10.1038/s42003-024-05888-1 · Cited by 21 · see citing works
Zhao, L., Gao, N., Peng, X., Chen, L., Meng, T., Jiang, C., Jin, J.-L., Zhang, J.-W., Duan, Q., Tian, H.-L., et al. (2024) · Advancement of science · doi:10.1002/advs.202301164 · Cited by 23 · see citing works
Defective Lamtor5 Leads to Autoimmunity by Deregulating v‐ATPase and Lysosomal Acidification
Zhang, W. K., Sha, Z., Tang, Y., Jin, C., Gao, W., Chen, C., Yu, L., Lv, N., Liu, S., Xu, F., et al. (2024) · Advanced Science · doi:10.1002/advs.202400446 · Cited by 16 · see citing works
Targeting mTOR Kinase for Cancer Treatment: A Comprehensive Review With Clinical Insights
Hossain, M. T., & Hossain, M. A. (2025) · Drug development research (Print) · doi:10.1002/ddr.70167 · Cited by 15 · see citing works
Block, M. R., Brunner, M., Ziegelmeyer, T., Lallemand, D., Pezet, M., Chevalier, G., Rondé, P., Gauthier‐Rouvière, C., Wehrle‐Haller, B., & Bouvard, D. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra120.013503 · Cited by 16 · see citing works
Ying, L., Zhang, M., Ma, X., Si, Y., Li, X., Su, J., Yin, J., & Bao, Y. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.672032 · Cited by 13 · see citing works
Signal integration in the (m)TORC1 growth pathway
Ramlaul, K., & Aylett, C. H. S. (2018) · Frontiers in Biology · doi:10.1007/s11515-018-1501-7 · Cited by 12 · see citing works
Lysosomes as hubs of metabolic sensing and cellular homeostasis.
Jain, A., & Zoncu, R. (2026) · Molecules and Cells · doi:10.1016/j.molcel.2026.01.011 · Cited by 11 · see citing works
Encoding Allostery in mTOR Signaling: The Structure of the Rag GTPase/Ragulator Complex
Cherfils, J. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.11.027 · Cited by 12 · see citing works
C7orf59/LAMTOR4 phosphorylation and structural flexibility modulate Ragulator assembly
Rasheed, N., Lima, T. B., Mercaldi, G. F., Nascimento, A. F. Z., Silva, A. L. S., Righetto, G. L., Bar‐Peled, L., Shen, K., Sabatini, D. M., Gozzo, F. C., et al. (2019) · FEBS Open Bio · doi:10.1002/2211-5463.12700 · Cited by 12 · see citing works
Jain, V., Bose, S. N., Arya, A. K., & Arif, T. (2022) · Cancers · doi:10.3390/cancers14071618 · Cited by 10 · see citing works
RetractedOdegaard, K. E., Gallegos, G., Koul, S., Schaal, V. L., Vellichirammal, N. N., Guda, C., Dutoit, A. P., Lisco, S. J., Yelamanchili, S. V., & Pendyala, G. (2022) · Cells · doi:10.3390/cells11111740 · Cited by 11 · see citing works
Powell, J. T., Kayesh, R., Ballesteros-Perez, A., Alam, K., Niyonshuti, P., Soderblom, E. J., Ding, K., Xu, C., & Yue, W. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics16010063 · Cited by 10 · see citing works
Dezan, E., van Stiphout, R., Gapp, B. V., Blomen, V., Brummelkamp, T., & Nijman, S. (2020) · Science Signaling · doi:10.1126/scisignal.aba5665 · Cited by 9 · see citing works
LAMTOR2 (p14) Controls B Cell Differentiation by Orchestrating Endosomal BCR Trafficking
Łyszkiewicz, M., Kotlarz, D., Ziętara, N., Brandes, G., Diestelhorst, J., Glage, S., Hobeika, E., Reth, M. G., Huber, L. A., Krueger, A., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00497 · Cited by 9 · see citing works
Self-citationZhang, J., Sun, B., Ruan, X., Hou, X., Zhi, J., Meng, X., Zheng, X., & Gao, M. (2021) · Cancer Biology and Medicine · doi:10.20892/j.issn.2095-3941.2020.0098 · Cited by 9 · see citing works
Ragopathies and the rising influence of RagGTPases on human diseases
Sambri, I., Ferniani, M., & Ballabio, A. (2024) · Nature Communications · doi:10.1038/s41467-024-50034-4 · Cited by 7 · see citing works
Finding new edges: systems approaches to MTOR signaling
Heberle, A. M., Rehbein, U., Rodríguez-Peiris, M., & Thedieck, K. (2021) · Biochemical Society Transactions · doi:10.1042/bst20190730 · Cited by 8 · see citing works
Peripheral lysosomes recruit PLEKHG3 to focal adhesions and restrain protrusion dynamics
Ettelt, R., Șandru, A.-M., Vucak, G., Didusch, S., Riemelmoser, B., Ehrenreiter, K., Hartl, M., Huber, L. A., & Baccarini, M. (2026) · FEBS Letters · doi:10.1002/1873-3468.70428 · Cited by 8 · see citing works
Self-citationCodependencies of mTORC1 signaling and endolysosomal actin structures
Priya, A., Antoine‐Bally, S., Macé, A., Monteiro, P., Sabatet, V., Remy, D., Dingli, F., Loew, D., Demetriades, C., Gautreau, A. M., et al. (2023) · Science Advances · doi:10.1126/sciadv.add9084 · Cited by 7 · see citing works
Yong, X., Jia, G., Yang, Q., Zhou, C., Zhang, S., Deng, H., Billadeau, D. D., Su, Z., & Jia, D. (2025) · Nature Communications · doi:10.1038/s41467-025-58235-1 · Cited by 7 · see citing works
Klee, K. M., Hess, M. W., Lohmüller, M., Herzog, S., Pfaller, K., Müller, T., Vogel, G. F., & Huber, L. A. (2023) · eLife · doi:10.7554/elife.80135 · Cited by 7 · see citing works
Self-citationMultiomic analysis reveals a key BCAT1 role in mTOR activation by B cell receptor and TLR9
Guo, R., Sun, Y., Lim, M. Y., Shah, H., Paulo, J. A., Ahmed, R. A., Li, W., Zhang, Y., Yang, H., Wang, L. W., et al. (2025) · Journal of Clinical Investigation · doi:10.1172/jci186258 · Cited by 8 · see citing works
How mTORC1 makes sense of nutrients
Luciani, A., & Stagi, M. (2020) · Kidney International · doi:10.1016/j.kint.2020.07.052 · Cited by 6 · see citing works
CASTOR1 and CASTOR2 respond to different arginine levels to regulate mTORC1 activity.
Liu, C., Zhang, Y., Wang, Y., Wu, M., Li, Y.-C., Wei, J., Shi, J., Wang, R., Su, L., Yang, T., et al. (2026) · Molecules and Cells · doi:10.1016/j.molcel.2025.12.016 · Cited by 6 · see citing works
EGO complex at 20: The Rag GTPase-TORC1 nutrient-sensing blueprint.
Virgilio, C. D. (2026) · Molecules and Cells · doi:10.1016/j.molcel.2025.12.018 · Cited by 6 · see citing works
Song, J., Wang, B., Zou, M., Zhou, H., Ding, Y., Ren, W., Fang, L., & Zhang, J. (2025) · Biology · doi:10.3390/biology14050477 · Cited by 5 · see citing works
Amino Acid Sensing: Architecture of mTORC1 on the Lysosome Surface
Peng, W., & Jewell, J. L. (2020) · Current Biology · doi:10.1016/j.cub.2019.11.087 · Cited by 5 · see citing works
Understanding P-Rex regulation: structural breakthroughs and emerging perspectives
Jones, G., & Ellisdon, A. M. (2024) · Biochemical Society Transactions · doi:10.1042/bst20231546 · Cited by 4 · see citing works
Wang, D., Zou, S., Ding, J., Gao, C., Wang, J., & Tang, Z. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2025.1665056 · Cited by 4 · see citing works
[New structures of mTORC1: Focus on Rag GTPases].
Nawrotek, A., & Cherfils, J. (2021) · Medecine sciences : M/S · doi:10.1051/medsci/2021033 · Cited by 4 · see citing works
Zhao, C.-S., Liu, S., Li, Z., Chen, J.-Y., & Xiong, X. (2025) · Cells · doi:10.3390/cells14131032 · Cited by 3 · see citing works
Reversing an agonist into an inhibitor: Development of mTOR degraders
Zhu, L., Fu, S., Ma, L., Chen, Z., Zeng, Q., Li, R., Zhou, Y., Qian, H., Meng, X., & Ge, J. (2025) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2025.117774 · Cited by 3 · see citing works
Genetic dissection of Ragulator structure and function in amino acid-dependent regulation of mTORC1.
Nada, S., & Okada, M. (2020) · Journal of Biochemistry (Tokyo) · doi:10.1093/jb/mvaa076 · Cited by 2 · see citing works
Hayatine inhibits amino acid-induced mTORC1 activation as a novel mTOR-Rag A/C interaction disruptor
Lü, M., Yu, L., Yang, Y., Zhu, J., Qiang, S., Wang, X., Wang, J., Tan, X., Wang, W.-F., Zhang, Y., et al. (2021) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2021.10.014 · Cited by 3 · see citing works
Structural Exploration on Palmitoyltransferase DHHC3 from Homo sapiens
Tang, M., Xia, Y., Xiao, T., Cao, R., Cao, Y., & OuYang, B. (2022) · Polymers · doi:10.3390/polym14153013 · Cited by 3 · see citing works
- Authors
- de Araujo, M. E. G., Naschberger, A., Fürnrohr, B. G., Stasyk, T., Dunzendorfer-Matt, T., Lechner, S., Welti, S., Kremser, L., Shivalingaiah, G., Offterdinger, M., Lindner, H. H., Huber, L. A., & Scheffzek, K.
- Affiliations
- Division of Cell Biology, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria.
- Innsbruck Medical University (AT)
- Corresponding author
- Naschberger, Andreas
- Fürnrohr, Barbara G.
- Huber, Lukas A.
- Scheffzek, Klaus
- ORCID
- Venue
- Science
- Published
- 2017-10-20
- Volume
- 358
- Issue
- 6361
- Pages
- 377-381
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2757150230
- Cited by
- 134
- References
- 61
- Citations by year
- 2026: 13 · 2025: 11 · 2024: 13 · 2023: 11 · 2022: 20 · 2021: 14 · 2020: 15 · 2019: 19 · 2018: 9 · 2017: 9
- FWCI
- 5.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Austrian Science Fund (award337283, P26682, award337284, P28975)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- Ragulator complex, mTORC1, LAMTOR1, Rag GTPases, lysosomes, heterodimer assembly, mTOR signaling, crystal structure, protein complex formation
- MeSH terms
- Protein Domains, Mechanistic Target of Rapamycin Complex 1, Carrier Proteins, Humans, Lysosomes, Signal Transduction, Crystallography, X-Ray, GTP Phosphohydrolases, Intracellular Signaling Peptides and Proteins
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