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| | ==Crystal structure of the arabidopsis thaliana Raptor in complex with the TOS peptide of human 4EBP1== | | ==Crystal structure of the arabidopsis thaliana Raptor in complex with the TOS peptide of human 4EBP1== |
| - | <StructureSection load='5wbj' size='340' side='right' caption='[[5wbj]], [[Resolution|resolution]] 3.00Å' scene=''> | + | <StructureSection load='5wbj' size='340' side='right'caption='[[5wbj]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5wbj]] is a 2 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=5WBJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WBJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5wbj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Arabidopsis_thaliana Arabidopsis thaliana] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WBJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WBJ 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=5wbj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wbj OCA], [http://pdbe.org/5wbj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wbj RCSB], [http://www.ebi.ac.uk/pdbsum/5wbj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wbj 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=5wbj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wbj OCA], [https://pdbe.org/5wbj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wbj RCSB], [https://www.ebi.ac.uk/pdbsum/5wbj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wbj 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> [[http://www.uniprot.org/uniprot/4EBP1_HUMAN 4EBP1_HUMAN]] Regulates eIF4E activity by preventing its assembly into the eIF4F complex. Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways.<ref>PMID:7935836</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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5wbj" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5wbj" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Raptor|Raptor]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Arath]] | + | [[Category: Arabidopsis thaliana]] |
| - | [[Category: Jiang, X]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Pavletich, N P]] | + | [[Category: Large Structures]] |
| - | [[Category: Protein binding]] | + | [[Category: Jiang X]] |
| - | [[Category: Raptor]] | + | [[Category: Pavletich NP]] |
| - | [[Category: To]]
| + | |
| Structural highlights
Function
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.[1]
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.
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Mahfouz MM, Kim S, Delauney AJ, Verma DP. Arabidopsis TARGET OF RAPAMYCIN interacts with RAPTOR, which regulates the activity of S6 kinase in response to osmotic stress signals. Plant Cell. 2006 Feb;18(2):477-90. doi: 10.1105/tpc.105.035931. Epub 2005 Dec 23. PMID:16377759 doi:http://dx.doi.org/10.1105/tpc.105.035931
- ↑ Yang H, Jiang X, Li B, Yang HJ, Miller M, Yang A, Dhar A, Pavletich NP. Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40. Nature. 2017 Dec 13. pii: nature25023. doi: 10.1038/nature25023. PMID:29236692 doi:http://dx.doi.org/10.1038/nature25023
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