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3fbv

From Proteopedia

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Current revision

Crystal structure of the oligomer formed by the kinase-ribonuclease domain of Ire1

Structural highlights

3fbv is a 14 chain structure with sequence from Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.2Å
Ligands:	, ,
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]

Publication Abstract from PubMed

Aberrant folding of proteins in the endoplasmic reticulum activates the bifunctional transmembrane kinase/endoribonuclease Ire1. Ire1 excises an intron from HAC1 messenger RNA in yeasts and Xbp1 messenger RNA in metozoans encoding homologous transcription factors. This non-conventional mRNA splicing event initiates the unfolded protein response, a transcriptional program that relieves the endoplasmic reticulum stress. Here we show that oligomerization is central to Ire1 function and is an intrinsic attribute of its cytosolic domains. We obtained the 3.2-A crystal structure of the oligomer of the Ire1 cytosolic domains in complex with a kinase inhibitor that acts as a potent activator of the Ire1 RNase. The structure reveals a rod-shaped assembly that has no known precedence among kinases. This assembly positions the kinase domain for trans-autophosphorylation, orders the RNase domain, and creates an interaction surface for binding of the mRNA substrate. Activation of Ire1 through oligomerization expands the mechanistic repertoire of kinase-based signalling receptors.

The unfolded protein response signals through high-order assembly of Ire1.,Korennykh AV, Egea PF, Korostelev AA, Finer-Moore J, Zhang C, Shokat KM, Stroud RM, Walter P Nature. 2009 Feb 5;457(7230):687-93. Epub 2008 Dec 14. PMID:19079236^[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
↑ Korennykh AV, Egea PF, Korostelev AA, Finer-Moore J, Zhang C, Shokat KM, Stroud RM, Walter P. The unfolded protein response signals through high-order assembly of Ire1. Nature. 2009 Feb 5;457(7230):687-93. Epub 2008 Dec 14. PMID:19079236 doi:nature07661

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3fbv"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the oligomer formed by the kinase-ribonuclease domain of Ire1==
-<StructureSection load='3fbv' size='340' side='right' caption='[[3fbv]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
+<StructureSection load='3fbv' size='340' side='right'caption='[[3fbv]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3fbv]] 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=3FBV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3FBV FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3fbv]] 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=3FBV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FBV 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]] 3.2&#8491;</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='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 Saccharomyces cerevisiae])</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=3fbv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fbv OCA], [https://pdbe.org/3fbv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fbv RCSB], [https://www.ebi.ac.uk/pdbsum/3fbv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fbv ProSAT]</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=3fbv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fbv OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3fbv RCSB], [http://www.ebi.ac.uk/pdbsum/3fbv PDBsum]</span></td></tr>
 </table>
 == 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;">
 == Publication Abstract from PubMed ==
@@ Line 18: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3fbv" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 25: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Saccharomyces cerevisiae]]
+[[Category: Large Structures]]
-[[Category: Egea, P F]]
+[[Category: Saccharomyces cerevisiae S288C]]
-[[Category: Finer-Moore, J]]
+[[Category: Egea PF]]
-[[Category: Korennykh, A V]]
+[[Category: Finer-Moore J]]
-[[Category: Korostelev, A A]]
+[[Category: Korennykh AV]]
-[[Category: Shokat, K M]]
+[[Category: Korostelev AA]]
-[[Category: Stroud, R M]]
+[[Category: Shokat KM]]
-[[Category: Walter, P]]
+[[Category: Stroud RM]]
-[[Category: Zhang, C]]
+[[Category: Walter P]]
-[[Category: Aminopyrazole]]
+[[Category: Zhang C]]
-[[Category: Apy29]]
-[[Category: Atp-binding]]
-[[Category: Complex]]
-[[Category: Cytoplasmic]]
-[[Category: Endoplasmic reticulum]]
-[[Category: Glycoprotein]]
-[[Category: Hydrolase]]
-[[Category: Inhibitor]]
-[[Category: Ire1]]
-[[Category: Kinase]]
-[[Category: Magnesium]]
-[[Category: Membrane]]
-[[Category: Metal-binding]]
-[[Category: Multifunctional enzyme]]
-[[Category: Nucleotide-binding]]
-[[Category: Oligomer]]
-[[Category: Phosphoprotein]]
-[[Category: Ribonuclease]]
-[[Category: Rnase]]
-[[Category: Serine/threonine-protein kinase]]
-[[Category: Transcription]]
-[[Category: Transcription regulation]]
-[[Category: Transferase]]
-[[Category: Transmembrane]]
-[[Category: Unfolded protein response]]

3fbv

From Proteopedia

Current revision

Crystal structure of the oligomer formed by the kinase-ribonuclease domain of Ire1

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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