6w3b: Difference between revisions
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<StructureSection load='6w3b' size='340' side='right'caption='[[6w3b]], [[Resolution|resolution]] 2.57Å' scene=''> | <StructureSection load='6w3b' size='340' side='right'caption='[[6w3b]], [[Resolution|resolution]] 2.57Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6w3b]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6w3b]] is a 1 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=6W3B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6W3B FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.57Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6w3b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w3b OCA], [https://pdbe.org/6w3b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6w3b RCSB], [https://www.ebi.ac.uk/pdbsum/6w3b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6w3b ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/ERN1_HUMAN ERN1_HUMAN] Senses unfolded proteins in the lumen of the endoplasmic reticulum via its N-terminal domain which leads to enzyme auto-activation. The active endoribonuclease domain splices XBP1 mRNA to generate a new C-terminus, converting it into a potent unfolded-protein response transcriptional activator and triggering growth arrest and apoptosis.<ref>PMID:9637683</ref> <ref>PMID:11175748</ref> <ref>PMID:12637535</ref> [UniProtKB:Q9EQY0] | ||
<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 6w3b" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 6w3b" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Ire1|Ire1]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Ferri | [[Category: Ferri E]] | ||
[[Category: Mortara | [[Category: Mortara K]] | ||
[[Category: Rudolph | [[Category: Rudolph J]] | ||
[[Category: Wallweber | [[Category: Wallweber H]] | ||
[[Category: Wang | [[Category: Wang W]] | ||
Latest revision as of 17:15, 18 October 2023
Structure of apo unphosphorylated IRE1Structure of apo unphosphorylated IRE1
Structural highlights
FunctionERN1_HUMAN Senses unfolded proteins in the lumen of the endoplasmic reticulum via its N-terminal domain which leads to enzyme auto-activation. The active endoribonuclease domain splices XBP1 mRNA to generate a new C-terminus, converting it into a potent unfolded-protein response transcriptional activator and triggering growth arrest and apoptosis.[1] [2] [3] [UniProtKB:Q9EQY0] Publication Abstract from PubMedInositol-Requiring Enzyme 1 (IRE1) is an essential component of the Unfolded Protein Response. IRE1 spans the endoplasmic reticulum membrane, comprising a sensory lumenal domain, and tandem kinase and endoribonuclease (RNase) cytoplasmic domains. Excess unfolded proteins in the ER lumen induce dimerization and oligomerization of IRE1, triggering kinase trans-autophosphorylation and RNase activation. Known ATP-competitive small-molecule IRE1 kinase inhibitors either allosterically disrupt or stabilize the active dimeric unit, accordingly inhibiting or stimulating RNase activity. Previous allosteric RNase activators display poor selectivity and/or weak cellular activity. In this study, we describe a class of ATP-competitive RNase activators possessing high selectivity and strong cellular activity. This class of activators binds IRE1 in the kinase front pocket, leading to a distinct conformation of the activation loop. Our findings reveal exquisitely precise interdomain regulation within IRE1, advancing the mechanistic understanding of this important enzyme and its investigation as a potential small-molecule therapeutic target. Activation of the IRE1 RNase through remodeling of the kinase front pocket by ATP-competitive ligands.,Ferri E, Le Thomas A, Wallweber HA, Day ES, Walters BT, Kaufman SE, Braun MG, Clark KR, Beresini MH, Mortara K, Chen YA, Canter B, Phung W, Liu PS, Lammens A, Ashkenazi A, Rudolph J, Wang W Nat Commun. 2020 Dec 14;11(1):6387. doi: 10.1038/s41467-020-19974-5. PMID:33318494[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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