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| | ==Structure of RNase-inactive point mutant of oligomeric kinase/RNase Ire1== | | ==Structure of RNase-inactive point mutant of oligomeric kinase/RNase Ire1== |
| - | <StructureSection load='3sdj' size='340' side='right' caption='[[3sdj]], [[Resolution|resolution]] 3.65Å' scene=''> | + | <StructureSection load='3sdj' size='340' side='right'caption='[[3sdj]], [[Resolution|resolution]] 3.65Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3sdj]] is a 14 chain structure with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SDJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SDJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3sdj]] is a 14 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SDJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SDJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=APJ:N~2~-1H-BENZIMIDAZOL-5-YL-N~4~-(3-CYCLOPROPYL-1H-PYRAZOL-5-YL)PYRIMIDINE-2,4-DIAMINE'>APJ</scene></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]] 3.65Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=APJ:N~2~-1H-BENZIMIDAZOL-5-YL-N~4~-(3-CYCLOPROPYL-1H-PYRAZOL-5-YL)PYRIMIDINE-2,4-DIAMINE'>APJ</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3sdm|3sdm]], [[3fbv|3fbv]]</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=3sdj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sdj OCA], [https://pdbe.org/3sdj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3sdj RCSB], [https://www.ebi.ac.uk/pdbsum/3sdj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3sdj ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IRE1, ERN1, YHR079C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae])</td></tr>
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| - | <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=3sdj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sdj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3sdj RCSB], [http://www.ebi.ac.uk/pdbsum/3sdj PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/IRE1_YEAST 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.<ref>PMID:8663458</ref> <ref>PMID:8670804</ref> <ref>PMID:9323131</ref> | + | [https://www.uniprot.org/uniprot/IRE1_YEAST 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.<ref>PMID:8663458</ref> <ref>PMID:8670804</ref> <ref>PMID:9323131</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 3sdj" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Saccharomyces cerevisiae]] | + | [[Category: Large Structures]] |
| - | [[Category: Egea, P]] | + | [[Category: Saccharomyces cerevisiae S288C]] |
| - | [[Category: Finer-Moore, J]] | + | [[Category: Egea P]] |
| - | [[Category: Korennykh, A]] | + | [[Category: Finer-Moore J]] |
| - | [[Category: Korostelev, A]] | + | [[Category: Korennykh A]] |
| - | [[Category: Shokat, K]] | + | [[Category: Korostelev A]] |
| - | [[Category: Stroud, R]] | + | [[Category: Shokat K]] |
| - | [[Category: Walter, P]] | + | [[Category: Stroud R]] |
| - | [[Category: Zhang, C]] | + | [[Category: Walter P]] |
| - | [[Category: Hac1]]
| + | [[Category: Zhang C]] |
| - | [[Category: Hydrolase]]
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| - | [[Category: Kinase]]
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| - | [[Category: Oligomer]]
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| - | [[Category: Ribonuclease]]
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| - | [[Category: Rna]]
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| - | [[Category: Rnase]]
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| - | [[Category: Splicing]]
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| - | [[Category: Transferase]]
| + | |
| - | [[Category: Unfolded protein response]]
| + | |
| - | [[Category: Upr]]
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| - | [[Category: Xbp1]]
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| Structural highlights
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]
Publication Abstract from PubMed
ABSTRACT: BACKGROUND: The unfolded protein response (UPR) controls the protein folding capacity of the endoplasmic reticulum (ER). Central to this signaling pathway is the ER-resident bifunctional transmembrane kinase/endoribonuclease Ire1. The endoribonuclease (RNase) domain of Ire1 initiates a non-conventional mRNA splicing reaction, leading to the production of a transcription factor that controls UPR target genes. The mRNA splicing reaction is an obligatory step of Ire1 signaling, yet, its mechanism has remained poorly understood due to the absence of substrate-bound crystal structures of Ire1, the lack of structural similarity between Ire1 and other RNases, and a scarcity of quantitative enzymological data. Here we experimentally define the active site of Ire1 RNase and quantitatively evaluate the contribution of the key active site residues to catalysis. RESULTS: This analysis and two new crystal structures suggest that Ire1 RNase uses histidine H1061 and tyrosine Y1043 as the general acid-general base pair contributing [greater than or equal to] 7.6 kcal/mol and 1.4 kcal/mol to transition state stabilization, respectively, and asparagine N1057 and arginine R1056 for coordination of the scissile phosphate. Investigation of the stem-loop recognition revealed that additionally to the stem-loops derived from the classic Ire1 substrates HAC1 and Xbp1 mRNA, Ire1 can site-specifically and rapidly cleave anticodon stem-loop (ASL) of unmodified tRNAPhe, extending known substrate specificity of Ire1 RNase. CONCLUSIONS: Our data define the catalytic center of Ire1 RNase and suggest a mechanism of RNA cleavage: each RNase monomer apparently contains a separate catalytic apparatus for RNA cleavage, whereas two RNase subunits contribute to RNA stem-loop docking. Conservation of the key residues among Ire1 homologues suggests that the mechanism elucidated here for yeast Ire1 applies to Ire1 in metazoan cells, and to the only known Ire1 homologue RNase L.
Structural and functional basis for RNA cleavage by Ire1.,Korennykh AV, Korostelev AA, Egea PF, Finer-Moore J, Stroud RM, Zhang C, Shokat KM, Walter P BMC Biol. 2011 Jul 6;9(1):47. PMID:21729333[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ Korennykh AV, Korostelev AA, Egea PF, Finer-Moore J, Stroud RM, Zhang C, Shokat KM, Walter P. Structural and functional basis for RNA cleavage by Ire1. BMC Biol. 2011 Jul 6;9(1):47. PMID:21729333 doi:10.1186/1741-7007-9-47
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