5wbj: Difference between revisions
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<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. 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 [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> | ||
</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> | </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> | ||
<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> | |||
</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> | [[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> | ||
<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. | |||
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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5wbj" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Arath]] | |||
[[Category: Jiang, X]] | [[Category: Jiang, X]] | ||
[[Category: Pavletich, N P]] | [[Category: Pavletich, N P]] | ||
Revision as of 09:39, 18 April 2018
Crystal structure of the arabidopsis thaliana Raptor in complex with the TOS peptide of human 4EBP1Crystal structure of the arabidopsis thaliana Raptor in complex with the TOS peptide of human 4EBP1
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] [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.[2] Publication Abstract from PubMedThe 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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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