Crystal Structure of the Gtr1pGTP-Gtr2pGDP Protein Complex Reveals Large Structural Rearrangements Triggered by GTP-to-GDP Conversion

作者: Jae-Hee Jeong , Kwang-Hoon Lee , Young-Mi Kim , Do-Hyung Kim , Byung-Ha Oh

DOI: 10.1074/JBC.C112.384420

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摘要: The heterodimeric Rag GTPases consisting of RagA (or RagB) and RagC RagD) are the key regulator activating target rapamycin complex 1 (TORC1) in response to level amino acids. heterodimer between GTP-loaded RagA/B GDP-loaded RagC/D is most active form that binds Raptor leads activation TORC1. Here, we present crystal structure Gtr1pGTP-Gtr2pGDP, yeast GTPase heterodimer. reveals GTP-to-GDP conversion on Gtr2p results a large conformational transition this subunit, including scale rearrangement long segment whose corresponding region involved binding Raptor. In addition, two domains brought contact with each other, but without causing any change Gtr1p subunit. These features explain how nucleotide-bound statuses subunits switch affinity off.

参考文章(20)
W.H. Brondyk, C.J. McKiernan, E.S. Burstein, I.G. Macara, Mutants of Rab3A analogous to oncogenic Ras mutants. Sensitivity to Rab3A-GTPase activating protein and Rab3A-guanine nucleotide releasing factor. Journal of Biological Chemistry. ,vol. 268, pp. 9410- 9415 ,(1993) , 10.1016/S0021-9258(18)98366-3
Lorenza Bordoli, Florian Kiefer, Konstantin Arnold, Pascal Benkert, James Battey, Torsten Schwede, Protein structure homology modeling using SWISS-MODEL workspace Nature Protocols. ,vol. 4, pp. 1- 13 ,(2009) , 10.1038/NPROT.2008.197
Takeshi Sekiguchi, Eiji Hirose, Nobutaka Nakashima, Miki Ii, Takeharu Nishimoto, Novel G Proteins, Rag C and Rag D, Interact with GTP-binding Proteins, Rag A and Rag B Journal of Biological Chemistry. ,vol. 276, pp. 7246- 7257 ,(2001) , 10.1074/JBC.M004389200
Xuemin Wang, Christopher G. Proud, Nutrient control of TORC1, a cell-cycle regulator. Trends in Cell Biology. ,vol. 19, pp. 260- 267 ,(2009) , 10.1016/J.TCB.2009.03.005
Axel T Brünger, Paul D Adams, G Marius Clore, Warren L DeLano, Piet Gros, Ralf W Grosse-Kunstleve, J-S Jiang, John Kuszewski, Michael Nilges, Navraj S Pannu, Randy J Read, Luke M Rice, Thomas Simonson, Gregory L Warren, Crystallography & NMR System: A New Software Suite for Macromolecular Structure Determination Acta Crystallographica Section D-biological Crystallography. ,vol. 54, pp. 905- 921 ,(1998) , 10.1107/S0907444998003254
Eunjung Kim, Pankuri Goraksha-Hicks, Li Li, Thomas P. Neufeld, Kun-Liang Guan, Regulation of TORC1 by Rag GTPases in nutrient response. Nature Cell Biology. ,vol. 10, pp. 935- 945 ,(2008) , 10.1038/NCB1753
John J Dumas, Zhongyuan Zhu, Joseph L Connolly, David G Lambright, Structural basis of activation and GTP hydrolysis in Rab proteins. Structure. ,vol. 7, pp. 413- 423 ,(1999) , 10.1016/S0969-2126(99)80054-9
D. Coleman, A. Berghuis, E Lee, M. Linder, A. Gilman, Sprang, Structures of active conformations of Gi alpha 1 and the mechanism of GTP hydrolysis. Science. ,vol. 265, pp. 1405- 1412 ,(1994) , 10.1126/SCIENCE.8073283
Iris Simon, Marino Zerial, Roger S. Goody, Kinetics of Interaction of Rab5 and Rab7 with Nucleotides and Magnesium Ions Journal of Biological Chemistry. ,vol. 271, pp. 20470- 20478 ,(1996) , 10.1074/JBC.271.34.20470