2rio: Difference between revisions

Revision as of 11:20, 7 October 2017

Structure of the dual enzyme Ire1 reveals the basis for catalysis and regulation of non-conventional splicing

Structural highlights

2rio is a 2 chain structure with sequence from Atcc 18824. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	ADP, MG, SR
Gene:	IRE1, ERN1 (ATCC 18824)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[IRE1_YEAST] 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 HAC1 precursor mRNA to produce the mature form which then induces transcription of UPR target genes.^[1] ^[2] ^[3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Ire1 is an ancient transmembrane sensor of ER stress with dual protein kinase and ribonuclease activities. In response to ER stress, Ire1 catalyzes the splicing of target mRNAs in a spliceosome-independent manner. We have determined the crystal structure of the dual catalytic region of Ire1at 2.4 A resolution, revealing the fusion of a domain, which we term the KEN domain, to the protein kinase domain. Dimerization of the kinase domain composes a large catalytic surface on the KEN domain which carries out ribonuclease function. We further show that signal induced trans-autophosphorylation of the kinase domain permits unfettered binding of nucleotide, which in turn promotes dimerization to compose the ribonuclease active site. Comparison of Ire1 to a topologically disparate ribonuclease reveals the convergent evolution of their catalytic mechanism. These findings provide a basis for understanding the mechanism of action of RNaseL and other pseudokinases, which represent 10% of the human kinome.

Structure of the dual enzyme Ire1 reveals the basis for catalysis and regulation in nonconventional RNA splicing.,Lee KP, Dey M, Neculai D, Cao C, Dever TE, Sicheri F Cell. 2008 Jan 11;132(1):89-100. PMID:18191223^[4]

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

References

↑ Welihinda AA, Kaufman RJ. The unfolded protein response pathway in Saccharomyces cerevisiae. Oligomerization and trans-phosphorylation of Ire1p (Ern1p) are required for kinase activation. J Biol Chem. 1996 Jul 26;271(30):18181-7. PMID:8663458
↑ Shamu CE, Walter P. Oligomerization and phosphorylation of the Ire1p kinase during intracellular signaling from the endoplasmic reticulum to the nucleus. EMBO J. 1996 Jun 17;15(12):3028-39. PMID:8670804
↑ Sidrauski C, Walter P. The transmembrane kinase Ire1p is a site-specific endonuclease that initiates mRNA splicing in the unfolded protein response. Cell. 1997 Sep 19;90(6):1031-9. PMID:9323131
↑ Lee KP, Dey M, Neculai D, Cao C, Dever TE, Sicheri F. Structure of the dual enzyme Ire1 reveals the basis for catalysis and regulation in nonconventional RNA splicing. Cell. 2008 Jan 11;132(1):89-100. PMID:18191223 doi:10.1016/j.cell.2007.10.057

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Welihinda AA, Kaufman RJ. The unfolded protein response pathway in Saccharomyces cerevisiae. Oligomerization and trans-phosphorylation of Ire1p (Ern1p) are required for kinase activation. J Biol Chem. 1996 Jul 26;271(30):18181-7. PMID:8663458

[2] Shamu CE, Walter P. Oligomerization and phosphorylation of the Ire1p kinase during intracellular signaling from the endoplasmic reticulum to the nucleus. EMBO J. 1996 Jun 17;15(12):3028-39. PMID:8670804

[3] Sidrauski C, Walter P. The transmembrane kinase Ire1p is a site-specific endonuclease that initiates mRNA splicing in the unfolded protein response. Cell. 1997 Sep 19;90(6):1031-9. PMID:9323131

[4] Lee KP, Dey M, Neculai D, Cao C, Dever TE, Sicheri F. Structure of the dual enzyme Ire1 reveals the basis for catalysis and regulation in nonconventional RNA splicing. Cell. 2008 Jan 11;132(1):89-100. PMID:18191223 doi:10.1016/j.cell.2007.10.057

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@@ Line 1: / Line 1: @@
 ==Structure of the dual enzyme Ire1 reveals the basis for catalysis and regulation of non-conventional splicing==
 <StructureSection load='2rio' size='340' side='right' caption='[[2rio]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SR:STRONTIUM+ION'>SR</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IRE1, ERN1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824])</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=2rio FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rio OCA], [http://pdbe.org/2rio PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2rio RCSB], [http://www.ebi.ac.uk/pdbsum/2rio PDBsum]</span></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=2rio FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rio OCA], [http://pdbe.org/2rio PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2rio RCSB], [http://www.ebi.ac.uk/pdbsum/2rio PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2rio ProSAT]</span></td></tr>
 </table>
 == Function ==

2rio: Difference between revisions

Revision as of 11:20, 7 October 2017

Structure of the dual enzyme Ire1 reveals the basis for catalysis and regulation of non-conventional splicing

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

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