6shc: Difference between revisions

Latest revision as of 12:41, 24 January 2024

Crystal structure of human IRE1 luminal domain Q105C

Structural highlights

6shc is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.55Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2] ^[3] [UniProtKB:Q9EQY0]

Publication Abstract from PubMed

Coupling of endoplasmic reticulum stress to dimerisationdependent activation of the UPR transducer IRE1 is incompletely understood. Whilst the luminal co-chaperone ERdj4 promotes a complex between the Hsp70 BiP and IRE1's stress-sensing luminal domain (IRE1(LD)) that favours the latter's monomeric inactive state and loss of ERdj4 de-represses IRE1, evidence linking these cellular and in vitro observations is presently lacking. We report that enforced loading of endogenous BiP onto endogenous IRE1alpha repressed UPR signalling in CHO cells and deletions in the IRE1alpha locus that de-repressed the UPR in cells, encode flexible regions of IRE1(LD) that mediated BiPinduced monomerisation in vitro. Changes in the hydrogen exchange mass spectrometry profile of IRE1(LD) induced by ERdj4 and BiP confirmed monomerisation and were consistent with active destabilisation of the IRE1(LD) dimer. Together, these observations support a competition model whereby waning ER stress passively partitions ERdj4 and BiP to IRE1(LD) to initiate active repression of UPR signalling.

Unstructured regions in IRE1alpha specify BiP-mediated destabilisation of the luminal domain dimer and repression of the UPR.,Amin-Wetzel N, Neidhardt L, Yan Y, Mayer MP, Ron D Elife. 2019 Dec 24;8. pii: 50793. doi: 10.7554/eLife.50793. PMID:31873072^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Tirasophon W, Welihinda AA, Kaufman RJ. A stress response pathway from the endoplasmic reticulum to the nucleus requires a novel bifunctional protein kinase/endoribonuclease (Ire1p) in mammalian cells. Genes Dev. 1998 Jun 15;12(12):1812-24. PMID:9637683
↑ Iwawaki T, Hosoda A, Okuda T, Kamigori Y, Nomura-Furuwatari C, Kimata Y, Tsuru A, Kohno K. Translational control by the ER transmembrane kinase/ribonuclease IRE1 under ER stress. Nat Cell Biol. 2001 Feb;3(2):158-64. PMID:11175748 doi:10.1038/35055065
↑ Liu CY, Xu Z, Kaufman RJ. Structure and intermolecular interactions of the luminal dimerization domain of human IRE1alpha. J Biol Chem. 2003 May 16;278(20):17680-7. Epub 2003 Mar 13. PMID:12637535 doi:10.1074/jbc.M300418200
↑ Amin-Wetzel N, Neidhardt L, Yan Y, Mayer MP, Ron D. Unstructured regions in IRE1alpha specify BiP-mediated destabilisation of the luminal domain dimer and repression of the UPR. Elife. 2019 Dec 24;8. pii: 50793. doi: 10.7554/eLife.50793. PMID:31873072 doi:https://dx.doi.org/10.7554/eLife.50793

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OCA

[1] Tirasophon W, Welihinda AA, Kaufman RJ. A stress response pathway from the endoplasmic reticulum to the nucleus requires a novel bifunctional protein kinase/endoribonuclease (Ire1p) in mammalian cells. Genes Dev. 1998 Jun 15;12(12):1812-24. PMID:9637683

[2] Iwawaki T, Hosoda A, Okuda T, Kamigori Y, Nomura-Furuwatari C, Kimata Y, Tsuru A, Kohno K. Translational control by the ER transmembrane kinase/ribonuclease IRE1 under ER stress. Nat Cell Biol. 2001 Feb;3(2):158-64. PMID:11175748 doi:10.1038/35055065

[3] Liu CY, Xu Z, Kaufman RJ. Structure and intermolecular interactions of the luminal dimerization domain of human IRE1alpha. J Biol Chem. 2003 May 16;278(20):17680-7. Epub 2003 Mar 13. PMID:12637535 doi:10.1074/jbc.M300418200

[4] Amin-Wetzel N, Neidhardt L, Yan Y, Mayer MP, Ron D. Unstructured regions in IRE1alpha specify BiP-mediated destabilisation of the luminal domain dimer and repression of the UPR. Elife. 2019 Dec 24;8. pii: 50793. doi: 10.7554/eLife.50793. PMID:31873072 doi:https://dx.doi.org/10.7554/eLife.50793

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[4]

@@ Line 3: / Line 3: @@
 <StructureSection load='6shc' size='340' side='right'caption='[[6shc]], [[Resolution|resolution]] 3.55&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6shc]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SHC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6SHC FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6shc]] 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=6SHC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SHC 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=6shc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6shc OCA], [http://pdbe.org/6shc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6shc RCSB], [http://www.ebi.ac.uk/pdbsum/6shc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6shc ProSAT]</span></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]] 3.55&#8491;</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=6shc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6shc OCA], [https://pdbe.org/6shc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6shc RCSB], [https://www.ebi.ac.uk/pdbsum/6shc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6shc ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://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]
+[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;">
 == Publication Abstract from PubMed ==
@@ Line 17: / Line 18: @@
 </div>
 <div class="pdbe-citations 6shc" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Ire1|Ire1]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Ron, D]]
+[[Category: Ron D]]
-[[Category: Yan, Y]]
+[[Category: Yan Y]]
-[[Category: Er stress]]
-[[Category: Ire1]]
-[[Category: Protein quality control]]
-[[Category: Signaling protein]]
-[[Category: Unfolded protein response]]

6shc: Difference between revisions

Latest revision as of 12:41, 24 January 2024

Crystal structure of human IRE1 luminal domain Q105C

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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