Crystal structure of the Gtr1pGTP-Gtr2pGDP protein complex reveals large structural rearrangements triggered by GTP-to-GDP conversion

Journal of Biological Chemistry

Volumn 287, Issue 35, 2012, Pages 29648-29653

  Jeong, Jae Hee ^a   Lee, Kwang Hoon ^b   Kim, Young Mi ^c   Kim, Do Hyung ^c   Oh, Byung Ha ^b   Kim, Yeon Gil ^a  

^a Pohang University of Science and Technology (POSTECH)   (South Korea)

^b Korea Advanced Institute of Science and Technology (KAIST)   (South Korea)

^c UNIVERSITY OF MINNESOTA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVE YEASTS; BINDING AFFINITIES; COMPLEX 1; CONFORMATIONAL CHANGE; CONFORMATIONAL TRANSITIONS; GTPASES; HETERODIMERS; KEY REGULATORS; PROTEIN COMPLEXES; SCALE REARRANGEMENTS; STRUCTURAL REARRANGEMENT; TARGET OF RAPAMYCIN;

AMINO ACIDS; BINDING ENERGY; CHEMICAL ACTIVATION;

BIOMOLECULES;

GUANOSINE DIPHOSPHATE; GUANOSINE TRIPHOSPHATASE; GUANOSINE TRIPHOSPHATE; MEMBRANE PROTEIN; PROTEIN GTR1P; PROTEIN GTRP; PROTEIN RAGA; PROTEIN RAPTOR; UNCLASSIFIED DRUG;

ARTICLE; BINDING AFFINITY; BINDING SITE; COMPLEX FORMATION; CONFORMATIONAL TRANSITION; CRYSTAL STRUCTURE; ENZYME ACTIVITY; ENZYME SUBUNIT; NONHUMAN; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN BINDING; PROTEIN DOMAIN; PROTEIN HYDROLYSIS; PROTEIN PROTEIN INTERACTION;

CRYSTALLOGRAPHY, X-RAY; GUANOSINE DIPHOSPHATE; GUANOSINE TRIPHOSPHATE; MONOMERIC GTP-BINDING PROTEINS; MULTIENZYME COMPLEXES; PROTEIN BINDING; PROTEIN STRUCTURE, QUATERNARY; SACCHAROMYCES CEREVISIAE; SACCHAROMYCES CEREVISIAE PROTEINS;

RAPTORES;

EID: 84865492819     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.C112.384420     Document Type: Article

References (20)

1. Wang, X., and Proud, C. G. (2009) Nutrient control of TORC1, a cell cycle regulator. Trends Cell Biol. 19, 260-267
2. Kim, E., Goraksha-Hicks, P., Li, L., Neufeld, T. P., and Guan, K. L. (2008) Regulation of TORC1 by Rag GTPases in nutrient response. Nat. Cell Biol. 10, 935-945
3. Sancak, Y., Peterson, T. R., Shaul, Y. D., Lindquist, R. A., Thoreen, C. C., Bar-Peled, L., and Sabatini, D. M. (2008) The Rag GTPases bind Raptor and mediate amino acid signaling to mTORC1. Science 320, 1496-1501
4. Sekiguchi, T., Hirose, E., Nakashima, N., Ii, M., and Nishimoto, T. (2001) Novel G proteins, Rag C and Rag D, interact with GTP-binding proteins, Rag A and Rag B. J. Biol. Chem. 276, 7246-7257
5. Binda, M., Péli-Gulli, M. P., Bonfils, G., Panchaud, N., Urban, J., Sturgill, T. W., Loewith, R., and De Virgilio, C. (2009) The Vam6 GEF controls TORC1 by activating the EGO complex. Mol. Cell 35, 563-573
6. Sancak, Y., Bar-Peled, L., Zoncu, R., Markhard, A. L., Nada, S., and Sabatini, D. M. (2010) Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell 141, 290-303
7. Gong, R., Li, L., Liu, Y., Wang, P., Yang, H., Wang, L., Cheng, J., Guan, K. L., and Xu, Y. (2011) Crystal structure of the Gtr1p-Gtr2p complex reveals new insights into the amino acid-induced TORC1 activation. Genes Dev. 25, 1668-1673
8. Terwilliger, T. C., Adams, P. D., Read, R. J., McCoy, A. J., Moriarty, N. W., Grosse-Kunstleve, R. W., Afonine, P. V., Zwart, P. H., and Hung, L. W. (2009) Decision-making in structure solution using Bayesian estimates of map quality: the PHENIX AutoSol wizard. Acta Crystallogr. D 65, 582-601
9. Emsley, P., and Cowtan, K. (2004) Coot: model-building tools for molecular graphics. Acta Crystallogr. D 60, 2126-2132
10. Brünger, A. T., Adams, P. D., Clore, G. M., DeLano, W. L., Gros, P., Grosse-Kunstleve, R. W., Jiang, J. S., Kuszewski, J., Nilges, M., Pannu, N. S., Read, R. J., Rice, L. M., Simonson, T., and Warren, G. L. (1998) Crystallography and NMR system: a new software suite for macromolecular structure determination. Acta Crystallogr. D Biol. Crystallogr. 54, 905-921
11. Rensland, H., Lautwein, A., Wittinghofer, A., and Goody, R. S. (1991) Is there a rate-limiting step before GTP cleavage by H-ras p21? Biochemistry 30, 11181-11185
12. Simon, I., Zerial, M., and Goody, R. S. (1996) Kinetics of interaction of Rab5 and Rab7 with nucleotides and magnesium ions. J. Biol. Chem. 271, 20470-20478
13. Schürmann, A., Brauers, A., Massmann, S., Becker, W., and Joost, H. G. (1995) Cloning of a novel family of mammalian GTP-binding proteins (RagA, RagBs, RagB1) with remote similarity to the Ras-related GTPases. J. Biol. Chem. 270, 28982-28988
14. Goldberg, J. (1998) Structural basis for activation of ARF GTPase: mechanisms of guanine nucleotide exchange and GTP-myristoyl switching. Cell 95, 237-248
15. Dumas, J. J., Zhu, Z., Connolly, J. L., and Lambright, D. G. (1999) Structural basis of activation and GTP hydrolysis in Rab proteins. Structure 7, 413-423
16. Pasqualato, S., Ménétrey, J., Franco, M., and Cherfils, J.(2001) The structural GDP/GTP cycle of human Arf6. EMBO Rep. 2, 234-238
17. Buhrman, G., Holzapfel, G., Fetics, S., and Mattos, C. (2010) Allosteric modulation of Ras positions Gln-61 for a direct role in catalysis. Proc. Natl. Acad. Sci. U.S.A. 107, 4931-4936
18. Brondyk, W. H., McKiernan, C. J., Burstein, E. S., and Macara, I. G. (1993) Mutants of Rab3A analogous to oncogenic Ras mutants: sensitivity to Rab3A-GTPase-activating protein and Rab3A-guanine nucleotide-releasing factor. J. Biol. Chem. 268, 9410-9415
19. 1 and the mechanism of GTP hydrolysis. Science 265, 1405-1412
20. Bordoli, L., Kiefer, F., Arnold, K., Benkert, P., Battey, J., and Schwede, T. (2009) Protein structure homology modeling using SWISS-MODEL workspace. Nat. Protoc. 4, 1-13