Structural Conservation of Components in the Amino Acid Sensing Branch of the TOR Pathway in Yeast and Mammals
Abstract
The highly conserved Rag family GTPases have a role in reporting amino acid availability to the TOR (target of rapamycin) signaling complex, which regulates cell growth and metabolism in response to environmental cues. The yeast Rag proteins Gtr1p and Gtr2p were shown in multiple independent studies to interact with the membrane-associated proteins Gse1p (Ego3p) and Gse2p (Ego1p). However, mammalian orthologs of Gse1p and Gse2p could not be identified. We determined the crystal structure of Gse1p and found it to match the fold of two mammalian proteins, MP1 (mitogen-activated protein kinase scaffold protein 1) and p14, which form a heterodimeric complex that had been assigned a scaffolding function in mitogen-activated protein kinase pathways. The significance of this structural similarity is validated by the recent identification of a physical and functional association between mammalian Rag proteins and MP1/p14. Together, these findings reveal that key components of the TOR signaling pathway are structurally conserved between yeast and mammals, despite divergence of sequence to a degree that thwarts detection through simple homology searches.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The structure of S. cerevisiae Ego3 provided evidence that the EGOC and Ragulator components are structurally conserved despite substantial sequence divergence, exhibiting a dimeric architecture very similar to that of LAMTOR2-LAMTOR3.
“The structure of S. cerevisiae Ego3 provided evidence that the EGOC and Ragulator components are structurally conserved, despite substantial sequence divergence (Kogan et al., 2010; Zhang et al., 2012), exhibiting a dimeric architecture very similar to that of LAMTOR2-LAMTOR3.”
From Signal integration in the (m)TORC1 growth pathway (2018) · cites this paper as Kogan et al., 2010
Cites
Sheldrick, G. M. (2007) · Acta Crystallographica Section A Foundations of Crystallography · doi:10.1107/s0108767307043930 · Cited by 87,861 · see citing works
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs
Altschul, S. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.17.3389 · Cited by 73,302 · see citing works
[20] Processing of X-ray diffraction data collected in oscillation mode
Otwinowski, Z., & Minor, W. (1997) · Methods in Enzymology · doi:10.1016/s0076-6879(97)76066-x · Cited by 33,475 · see citing works
<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
Crystallography & NMR System: A New Software Suite for Macromolecular Structure Determination
Brünger, A. T., Adams, P. D., Clore, G. M., DeLano, W. L., Gros, P., Grosse‐Kunstleve, R. W., Jiang, J., Kuszewski, J. J., Nilges, M., Pannu, N., et al. (1998) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444998003254 · Cited by 15,720 · see citing works
Kabsch, W., & Sander, C. (1983) · Biopolymers · doi:10.1002/bip.360221211 · Cited by 15,320 · 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
Murzin, A. G., Brenner, S. E., Hubbard, T., & Chothia, C. (1995) · Journal of Molecular Biology · doi:10.1016/s0022-2836(05)80134-2 · Cited by 6,412 · see citing works
Protein structure prediction on the Web: a case study using the Phyre server
Kelley, L. A., & Sternberg, M. J. E. (2009) · Nature Protocols · doi:10.1038/nprot.2009.2 · Cited by 4,154 · see citing works
MolProbity: all-atom contacts and structure validation for proteins and nucleic acids
Davis, I., Leaver‐Fay, A., Chen, V. B., Block, J. N., Kapral, G. J., Wang, X., Murray, L. W., Arendall, W. B., Snoeyink, J. S., Richardson, J. S., et al. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm216 · Cited by 3,915 · 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
Dosztányi, Z., Csizmók, V., Tompa, P., & Simon, I. (2005) · Computer applications in the biosciences · doi:10.1093/bioinformatics/bti541 · Cited by 1,943 · see citing works
Global Analysis of Protein Activities Using Proteome Chips
Zhu, H., Bilgin, M., Bangham, R., Hall, D., Casamayor, A., Bertone, P., Lan, N., Jansen, R., Bidlingmaier, S., Houfek, T., et al. (2001) · Science · doi:10.1126/science.1062191 · Cited by 1,884 · see citing works
The Ras superfamily at a glance
Wennerberg, K., Rossman, K. L., & Der, C. J. (2005) · Journal of Cell Science · doi:10.1242/jcs.01660 · Cited by 1,549 · see citing works
Rost, B., Yachdav, G., & Liu, J. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkh377 · Cited by 1,462 · see citing works
Atomic Structures of the Human Immunophilin FKBP-12 Complexes with FK506 and Rapamycin
Duyne, G. D. V., Standaert, R. F., Karplus, P. A., Schreiber, S. L., & Clardy, J. (1993) · Journal of Molecular Biology · doi:10.1006/jmbi.1993.1012 · Cited by 1,190 · see citing works
Searching protein structure databases with DaliLite v.3
Holm, L., Kääriäinen, S., Rosenström, P., & Schenkel, A. (2008) · Bioinformatics · doi:10.1093/bioinformatics/btn507 · Cited by 1,017 · see citing works
Systematic screen for human disease genes in yeast
Steinmetz, L. M., Scharfe, C., Deutschbauer, A. M., Mokranjac, D., Herman, Z. S., Jones, T., Chu, A. M., Giaever, G. N., Prokisch, H., Oefner, P. J., et al. (2002) · Nature Genetics · doi:10.1038/ng929 · Cited by 544 · see citing works
MP1: A MEK Binding Partner That Enhances Enzymatic Activation of the MAP Kinase Cascade
Schaeffer, H. J., Catling, A. D., Eblen, S. T., Collier, L. S., Krauss, A., & Weber, M. J. (1998) · Science · doi:10.1126/science.281.5383.1668 · Cited by 472 · see citing works
The Vam6 GEF Controls TORC1 by Activating the EGO Complex
Binda, M., Gulli, M., Bonfils, G., Panchaud, N., Urban, J., Sturgill, T. W., Loewith, R., & VIRGILIO, C. D. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.06.033 · Cited by 432 · see citing works
Peng, T., Golub, T. R., & Sabatini, D. M. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.15.5575-5584.2002 · Cited by 393 · 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
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
The TOR and EGO Protein Complexes Orchestrate Microautophagy in Yeast
Dubouloz, F., Deloche, O., Wanke, V., Cameroni, E., & VIRGILIO, C. D. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.05.020 · Cited by 336 · 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
Bohn, G., Saborowski, A. L., Brandes, G., Thiel, J., Glocker, E. O., Schäffer, A. A., Rathinam, C., Taub, N., Teis, D., Zeidler, C., et al. (2006) · Nature Medicine · doi:10.1038/nm1528 · Cited by 202 · see citing works
Wunderlich, W., Fialka, I., Teis, D., Alpi, A. F., Pfeifer, A. C., Parton, R. G., Lottspeich, F., & Huber, L. A. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.152.4.765 · Cited by 197 · see citing works
Gao, M., & Kaiser, C. A. (2006) · Nature Cell Biology · doi:10.1038/ncb1419 · Cited by 174 · see citing works
Self-citationProtein acrobatics in pairs — dimerization via domain swapping
Gronenborn, A. M. (2009) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2008.12.002 · Cited by 168 · see citing works
Darsow, T., Burd, C. G., & Emr, S. D. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.142.4.913 · Cited by 145 · see citing works
Schürmann, A., Brauers, A., Maßmann, S., Becker, W. B., & Joost, H. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.48.28982 · Cited by 118 · see citing works
Kurzbauer, 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
RagA is a functional homologue of S. cerevisiae Gtr1p involved in the Ran/Gsp1-GTPase pathway
Hirose, E., Nakashima, N., Sekiguchi, T., & Nishimoto, T. (1998) · Journal of Cell Science · doi:10.1242/jcs.111.1.11 · Cited by 89 · see citing works
Koonin, E. V., & Aravind, L. (2000) · Current Biology · doi:10.1016/s0960-9822(00)00774-0 · Cited by 88 · see citing works
Zurita-Martinez, S. A., Puria, R., Pan, X., Boeke, J. D., & Cardenas, M. E. (2007) · Genetics · doi:10.1534/genetics.107.072835 · Cited by 88 · see citing works
Rab6 family proteins interact with the dynein light chain protein DYNLRB1
Wanschers, B. F. J., van de Vorstenbosch, R. A., Wijers, M., Wieringa, B., King, S. M., & Fransen, J. A. M. (2007) · Cell Motility and the Cytoskeleton · doi:10.1002/cm.20254 · Cited by 80 · 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
ERS1 encodes a functional homologue of the human lysosomal cystine transporter
Gao, X., Wang, J., Keppler‐Ross, S., et al. (2005) · FEBS Journal · doi:10.1111/j.1742-4658.2005.04670.x · Cited by 52 · see citing works
Structure and Dynamics of the Homodimeric Dynein Light Chain km23
Ilangovan, U., Ding, W., Zhong, Y., Wilson, C. L., Groppe, J. C., Trbovich, J. T., Zúñiga, J. E., Demeler, B., Tang, Q., Gao, G., et al. (2005) · Journal of Molecular Biology · doi:10.1016/j.jmb.2005.07.002 · Cited by 35 · see citing works
An EGOcentric view of TORC1 signaling
Binda, M., Bonfils, G., Panchaud, N., et al. (2010) · Cell Cycle · doi:10.4161/cc.9.2.10585 · Cited by 18 · see citing works
Developmental strategies for evasion ofArftumor suppression
Volanakis, E. J., & Sherr, C. J. (2010) · Cell Cycle · doi:10.4161/cc.9.1.10390 · Cited by 4 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Amino acid signalling upstream of mTOR
Jewell, J. L., Russell, R. C., & Guan, K.-L. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3522 · Cited by 894 · see citing works
AMPK and TOR: The Yin and Yang of Cellular Nutrient Sensing and Growth Control
González, A., Hall, M. N., Lin, S.-C., & Hardie, D. G. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.01.015 · Cited by 797 · 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
Amino acids and mTORC1: from lysosomes to disease
Efeyan, A., Zoncu, R., & Sabatini, D. M. (2012) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2012.05.007 · Cited by 436 · see citing works
“N IH -PA Author M anuscript N IH -PA Author M anuscript N IH -PA Author M anuscript crystal structure of Ego2–3 was recently solved and found to be very similar to that of LAMTOR2–3 [46,47].”
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
Levine, T. P., Daniels, R. D., Wong, L. H., Gatta, A. T., Gerondopoulos, A., & Barr, F. A. (2013) · Small GTPases · doi:10.4161/sgtp.24262 · Cited by 93 · see citing works
Powis, 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
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
- Authors
- Kogan, K., Spear, E. D., Kaiser, C. A., & Fass, D.
- Affiliations
- Weizmann Institute of Science (IL)
- Massachusetts Institute of Technology (US)
- Corresponding author
- Fass, Deborah
- Venue
- Journal of Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2010-09
- Volume
- 402
- Issue
- 2
- Pages
- 388-398
- ISSN
- 0022-2836 (ISSN-L)
- OpenAlex
- W2056735058
- Cited by
- 56
- References
- 42
- Citations by year
- 2026: 1 · 2024: 1 · 2021: 1 · 2020: 3 · 2018: 4 · 2017: 5 · 2016: 3 · 2015: 5 · 2014: 8 · 2013: 10 · 2012: 8
- FWCI
- 3.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- TOR signaling, Rag GTPases, amino acid sensing, p14, structural conservation, protein crystal structure, cell growth regulation
- MeSH terms
- Amino Acid Sequence, Animals, Mammals, Membrane Proteins, Models, Molecular, Molecular Sequence Data, Protein Binding, Saccharomyces cerevisiae, Sequence Alignment, Conserved Sequence, Protein Structure, Secondary, Protein Structure, Tertiary, Crystallography, X-Ray, Saccharomyces cerevisiae Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
