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8dhb
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Active FLCN GAP complex== | |
| + | <StructureSection load='8dhb' size='340' side='right'caption='[[8dhb]], [[Resolution|resolution]] 3.53Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8dhb]] 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=8DHB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DHB FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BEF:BERYLLIUM+TRIFLUORIDE+ION'>BEF</scene>, <scene name='pdbligand=CZC:[(2~{R},3~{S},4~{R},5~{R})-5-[2,6-bis(oxidanylidene)-3~{H}-purin-9-yl]-3,4-bis(oxidanyl)oxolan-2-yl]methyl+phosphono+hydrogen+phosphate'>CZC</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</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=8dhb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dhb OCA], [https://pdbe.org/8dhb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dhb RCSB], [https://www.ebi.ac.uk/pdbsum/8dhb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dhb ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/RRAGC_HUMAN RRAGC_HUMAN]] Guanine nucleotide-binding protein forming heterodimeric Rag complexes required for the amino acid-induced relocalization of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB. This is a crucial step in the activation of the TOR signaling cascade by amino acids.<ref>PMID:20381137</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The mechanistic target of rapamycin complex 1 (mTORC1) regulates cell growth and catabolism in response to nutrients through phosphorylation of key substrates. The tumor suppressor folliculin (FLCN) is a RagC/D guanosine triphosphatase (GTPase)-activating protein (GAP) that regulates mTORC1 phosphorylation of MiT-TFE transcription factors, controlling lysosome biogenesis and autophagy. We determined the cryo-electron microscopy structure of the active FLCN complex (AFC) containing FLCN, FNIP2, the N-terminal tail of SLC38A9, the RagA(GDP):RagC(GDP.BeFx-) GTPase dimer, and the Ragulator scaffold. Relative to the inactive lysosomal FLCN complex structure, FLCN reorients by 90 degrees , breaks contact with RagA, and makes previously unseen contacts with RagC that position its Arg(164) finger for catalysis. Disruption of the AFC-specific interfaces of FLCN and FNIP2 with RagC eliminated GAP activity and led to nuclear retention of TFE3, with no effect on mTORC1 substrates S6K or 4E-BP1. The structure provides a basis for regulation of an mTORC1 substrate-specific pathway and a roadmap to discover MiT-TFE family selective mTORC1 antagonists. | ||
| - | + | Structural basis for FLCN RagC GAP activation in MiT-TFE substrate-selective mTORC1 regulation.,Jansen RM, Peruzzo R, Fromm SA, Yokom AL, Zoncu R, Hurley JH Sci Adv. 2022 Sep 16;8(37):eadd2926. doi: 10.1126/sciadv.add2926. Epub 2022 Sep, 14. PMID:36103527<ref>PMID:36103527</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8dhb" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Hurley JH]] | ||
| + | [[Category: Jansen RM]] | ||
Current revision
Active FLCN GAP complex
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