7t3a
From Proteopedia
(Difference between revisions)
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| - | ==== | + | ==GATOR1-RAG-RAGULATOR - Inhibitory Complex== |
| - | <StructureSection load='7t3a' size='340' side='right'caption='[[7t3a]]' scene=''> | + | <StructureSection load='7t3a' size='340' side='right'caption='[[7t3a]], [[Resolution|resolution]] 4.00Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7t3a]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7T3A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7T3A FirstGlance]. <br> |
| - | </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=7t3a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t3a OCA], [https://pdbe.org/7t3a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t3a RCSB], [https://www.ebi.ac.uk/pdbsum/7t3a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t3a ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4Å</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></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=7t3a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t3a OCA], [https://pdbe.org/7t3a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t3a RCSB], [https://www.ebi.ac.uk/pdbsum/7t3a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t3a ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/DEPD5_HUMAN DEPD5_HUMAN] Rolandic epilepsy;Autosomal dominant nocturnal frontal lobe epilepsy;Autosomal dominant epilepsy with auditory features;Familial focal epilepsy with variable foci. The disease is caused by mutations affecting the gene represented in this entry. Inactivating mutations and truncating deletions in the genes encoding GATOR1 proteins, including DEPDC5, are detected in glioblastoma and ovarian tumors and are associated with loss of heterozygosity events. Inactivation of GATOR1 proteins promotes constitutive localization of mTORC1 to the lysosomal membrane and blocks mTORC1 inactivation following amino acid withdrawal (PubMed:23723238).<ref>PMID:23723238</ref> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/DEPD5_HUMAN DEPD5_HUMAN] As a component of the GATOR1 complex functions as an inhibitor of the amino acid-sensing branch of the TORC1 pathway. The GATOR1 complex strongly increases GTP hydrolysis by RRAGA and RRAGB within RRAGC-containing heterodimers, thereby deactivating RRAGs, releasing mTORC1 from lysosomal surface and inhibiting mTORC1 signaling. The GATOR1 complex is negatively regulated by GATOR2 the other GATOR subcomplex in this amino acid-sensing branch of the TORC1 pathway.<ref>PMID:23723238</ref> <ref>PMID:25457612</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | mTORC1 controls cellular metabolic processes in response to nutrient availability. Amino acid signals are transmitted to mTORC1 through the Rag GTPases, which are localized on the lysosomal surface by the Ragulator complex. The Rag GTPases receive amino acid signals from multiple upstream regulators. One negative regulator, GATOR1, is a GTPase activating protein (GAP) for RagA. GATOR1 binds to the Rag GTPases via two modes: an inhibitory mode and a GAP mode. How these two binding interactions coordinate to process amino acid signals is unknown. Here, we resolved three cryo-EM structural models of the GATOR1-Rag-Ragulator complex, with the Rag-Ragulator subcomplex occupying the inhibitory site, the GAP site, and both binding sites simultaneously. When the Rag GTPases bind to GATOR1 at the GAP site, both Rag subunits contact GATOR1 to coordinate their nucleotide loading states. These results reveal a potential GAP mechanism of GATOR1 during the mTORC1 inactivation process. | ||
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| + | Cryo-EM structures of the human GATOR1-Rag-Ragulator complex reveal a spatial-constraint regulated GAP mechanism.,Egri SB, Ouch C, Chou HT, Yu Z, Song K, Xu C, Shen K Mol Cell. 2022 May 19;82(10):1836-1849.e5. doi: 10.1016/j.molcel.2022.03.002. , Epub 2022 Mar 25. PMID:35338845<ref>PMID:35338845</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7t3a" style="background-color:#fffaf0;"></div> | ||
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| + | ==See Also== | ||
| + | *[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]] | ||
| + | *[[Ragulator complex 3D structures|Ragulator complex 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Egri SB]] |
| + | [[Category: Shen K]] | ||
Current revision
GATOR1-RAG-RAGULATOR - Inhibitory Complex
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