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| | ==Crystal Structure of Gtr1p-Gtr2p complex== | | ==Crystal Structure of Gtr1p-Gtr2p complex== |
| - | <StructureSection load='3r7w' size='340' side='right' caption='[[3r7w]], [[Resolution|resolution]] 2.77Å' scene=''> | + | <StructureSection load='3r7w' size='340' side='right'caption='[[3r7w]], [[Resolution|resolution]] 2.77Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3r7w]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R7W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3R7W FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3r7w]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R7W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3R7W FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.773Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GTR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae]), GTR2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae])</td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3r7w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r7w OCA], [https://pdbe.org/3r7w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3r7w RCSB], [https://www.ebi.ac.uk/pdbsum/3r7w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3r7w ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3r7w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r7w OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3r7w RCSB], [http://www.ebi.ac.uk/pdbsum/3r7w PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/RAGAB_YEAST RAGAB_YEAST] GTPase involved in activation of the TORC1 signaling pathway, which promotes growth and represses autophagy in nutrient-rich conditions (PubMed:26510498, PubMed:28993463, PubMed:32801125). Also required for TORC1 inactivation during nitrogen starvation (PubMed:28993463). Required for intracellular sorting of GAP1 out of the endosome (PubMed:16732272). Functionally associated with the inorganic phosphate transporter PHO84, and may be involved in regulating its function or localization (PubMed:1620108).<ref>PMID:1620108</ref> <ref>PMID:16732272</ref> <ref>PMID:26510498</ref> <ref>PMID:28993463</ref> <ref>PMID:32801125</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 3r7w" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[GTP-binding protein|GTP-binding protein]] | + | *[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Saccharomyces cerevisiae]] | | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Cheng, J]] | + | [[Category: Cheng J]] |
| - | [[Category: Gong, R]] | + | [[Category: Gong R]] |
| - | [[Category: Guan, K L]] | + | [[Category: Guan KL]] |
| - | [[Category: Li, L]] | + | [[Category: Li L]] |
| - | [[Category: Liu, Y]] | + | [[Category: Liu Y]] |
| - | [[Category: Wang, L]] | + | [[Category: Wang L]] |
| - | [[Category: Wang, P]] | + | [[Category: Wang P]] |
| - | [[Category: Xu, Y]] | + | [[Category: Xu Y]] |
| - | [[Category: Yang, H]] | + | [[Category: Yang H]] |
| - | [[Category: Gtr1p]]
| + | |
| - | [[Category: Gtr2p]]
| + | |
| - | [[Category: Mtor]]
| + | |
| - | [[Category: Protein transport]]
| + | |
| - | [[Category: Rag gtpase]]
| + | |
| Structural highlights
Function
RAGAB_YEAST GTPase involved in activation of the TORC1 signaling pathway, which promotes growth and represses autophagy in nutrient-rich conditions (PubMed:26510498, PubMed:28993463, PubMed:32801125). Also required for TORC1 inactivation during nitrogen starvation (PubMed:28993463). Required for intracellular sorting of GAP1 out of the endosome (PubMed:16732272). Functionally associated with the inorganic phosphate transporter PHO84, and may be involved in regulating its function or localization (PubMed:1620108).[1] [2] [3] [4] [5]
Publication Abstract from PubMed
The target of rapamycin (TOR) complex 1 (TORC1) is a central cell growth regulator in response to a wide array of signals. The Rag GTPases play an essential role in relaying amino acid signals to TORC1 activation through direct interaction with raptor and recruitment of the TORC1 complex to lysosomes. Here we present the crystal structure of the Gtr1p-Gtr2p complex, the Rag homologs from Saccharomyces cerevisiae, at 2.8 A resolution. The heterodimeric GTPases reveal a pseudo-twofold symmetric organization. Structure-guided functional analyses of RagA-RagC, the human homologs of Gtr1p-Gtr2p, show that both G domains (N-terminal GTPase domains) and dimerization are important for raptor binding. In particular, the switch regions of the G domain in RagA are indispensible for interaction with raptor, and hence TORC1 activation. The dimerized C-terminal domains of RagA-RagC display a remarkable structural similarity to MP1/p14, which is in a complex with lysosome membrane protein p18, and directly interact with p18, therefore recruiting mTORC1 to the lysosome for activation by Rheb. Our results reveal a structural model for the mechanism of the Rag GTPases in TORC1 activation and amino acid signaling.
Crystal structure of the Gtr1p-Gtr2p complex reveals new insights into the amino acid-induced TORC1 activation.,Gong R, Li L, Liu Y, Wang P, Yang H, Wang L, Cheng J, Guan KL, Xu Y Genes Dev. 2011 Aug 15;25(16):1668-73. Epub 2011 Aug 4. PMID:21816923[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Bun-Ya M, Harashima S, Oshima Y. Putative GTP-binding protein, Gtr1, associated with the function of the Pho84 inorganic phosphate transporter in Saccharomyces cerevisiae. Mol Cell Biol. 1992 Jul;12(7):2958-66. PMID:1620108 doi:10.1128/mcb.12.7.2958-2966.1992
- ↑ Gao M, Kaiser CA. A conserved GTPase-containing complex is required for intracellular sorting of the general amino-acid permease in yeast. Nat Cell Biol. 2006 Jul;8(7):657-67. Epub 2006 May 28. PMID:16732272 doi:ncb1419
- ↑ Kim A, Cunningham KW. A LAPF/phafin1-like protein regulates TORC1 and lysosomal membrane permeabilization in response to endoplasmic reticulum membrane stress. Mol Biol Cell. 2015 Dec 15;26(25):4631-45. PMID:26510498 doi:10.1091/mbc.E15-08-0581
- ↑ Varlakhanova NV, Mihalevic MJ, Bernstein KA, Ford MGJ. Pib2 and the EGO complex are both required for activation of TORC1. J Cell Sci. 2017 Nov 15;130(22):3878-3890. PMID:28993463 doi:10.1242/jcs.207910
- ↑ Uemura S, Mochizuki T, Amemiya K, Kurosaka G, Yazawa M, Nakamoto K, Ishikawa Y, Izawa S, Abe F. Amino acid homeostatic control by TORC1 in Saccharomyces cerevisiae under high hydrostatic pressure. J Cell Sci. 2020 Sep 9;133(17):jcs245555. PMID:32801125 doi:10.1242/jcs.245555
- ↑ Gong R, Li L, Liu Y, Wang P, Yang H, Wang L, Cheng J, Guan KL, Xu Y. Crystal structure of the Gtr1p-Gtr2p complex reveals new insights into the amino acid-induced TORC1 activation. Genes Dev. 2011 Aug 15;25(16):1668-73. Epub 2011 Aug 4. PMID:21816923 doi:10.1101/gad.16968011
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