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| | ==Crystal structure of the Arabidopsis thaliana Raptor== | | ==Crystal structure of the Arabidopsis thaliana Raptor== |
| - | <StructureSection load='5wbi' size='340' side='right' caption='[[5wbi]], [[Resolution|resolution]] 3.00Å' scene=''> | + | <StructureSection load='5wbi' size='340' side='right'caption='[[5wbi]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5wbi]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Arath Arath]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WBI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WBI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5wbi]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Arabidopsis_thaliana Arabidopsis thaliana]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WBI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WBI FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RAPTOR1, RAPTOR1B, At3g08850, T16O11.22 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=3702 ARATH])</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]] 3Å</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=5wbi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wbi OCA], [http://pdbe.org/5wbi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wbi RCSB], [http://www.ebi.ac.uk/pdbsum/5wbi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wbi ProSAT]</span></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=5wbi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wbi OCA], [https://pdbe.org/5wbi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wbi RCSB], [https://www.ebi.ac.uk/pdbsum/5wbi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wbi ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RTOR1_ARATH RTOR1_ARATH]] Probable component of the plant TOR kinase pathway that recruits substrates for TOR. Modulates plant cell growth and regulates the activity of ATPK1 kinase in response to osmotic stress.<ref>PMID:16377759</ref> | + | [https://www.uniprot.org/uniprot/RTOR1_ARATH RTOR1_ARATH] Probable component of the plant TOR kinase pathway that recruits substrates for TOR. Modulates plant cell growth and regulates the activity of ATPK1 kinase in response to osmotic stress.<ref>PMID:16377759</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | The mechanistic target of rapamycin complex 1 (mTORC1) controls cell growth and metabolism in response to nutrients, energy levels, and growth factors. It contains the atypical kinase mTOR and the RAPTOR subunit that binds to the Tor signalling sequence (TOS) motif of substrates and regulators. mTORC1 is activated by the small GTPase RHEB (Ras homologue enriched in brain) and inhibited by PRAS40. Here we present the 3.0 angstrom cryo-electron microscopy structure of mTORC1 and the 3.4 angstrom structure of activated RHEB-mTORC1. RHEB binds to mTOR distally from the kinase active site, yet causes a global conformational change that allosterically realigns active-site residues, accelerating catalysis. Cancer-associated hyperactivating mutations map to structural elements that maintain the inactive state, and we provide biochemical evidence that they mimic RHEB relieving auto-inhibition. We also present crystal structures of RAPTOR-TOS motif complexes that define the determinants of TOS recognition, of an mTOR FKBP12-rapamycin-binding (FRB) domain-substrate complex that establishes a second substrate-recruitment mechanism, and of a truncated mTOR-PRAS40 complex that reveals PRAS40 inhibits both substrate-recruitment sites. These findings help explain how mTORC1 selects its substrates, how its kinase activity is controlled, and how it is activated by cancer-associated mutations.
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| - | Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40.,Yang H, Jiang X, Li B, Yang HJ, Miller M, Yang A, Dhar A, Pavletich NP Nature. 2017 Dec 13. pii: nature25023. doi: 10.1038/nature25023. PMID:29236692<ref>PMID:29236692</ref>
| + | ==See Also== |
| - | | + | *[[Raptor 3D structures|Raptor 3D structures]] |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 5wbi" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Arath]] | + | [[Category: Arabidopsis thaliana]] |
| - | [[Category: Jiang, X]] | + | [[Category: Large Structures]] |
| - | [[Category: Pavletich, N P]] | + | [[Category: Jiang X]] |
| - | [[Category: Frb]] | + | [[Category: Pavletich NP]] |
| - | [[Category: Protein binding]]
| + | |
