View source for 3sdm


==Structure of oligomeric kinase/RNase Ire1 in complex with an oligonucleotide==
<StructureSection load='3sdm' size='340' side='right' caption='[[3sdm]], [[Resolution|resolution]] 6.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3sdm]] is a 7 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SDM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SDM FirstGlance]. <br>
</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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3fbv|3fbv]], [[3sdj|3sdj]]</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=559292 Baker's yeast])</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=3sdm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sdm OCA], [http://pdbe.org/3sdm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3sdm RCSB], [http://www.ebi.ac.uk/pdbsum/3sdm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3sdm ProSAT]</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>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
ABSTRACT: BACKGROUND: Ire1 is a signal transduction protein in the endoplasmic reticulum (ER) membrane that serves to adjust the protein-folding capacity of the ER according to the needs of the cell. Ire1 signals in a transcriptional program, the "unfolded protein response" (UPR), via the coordinated action of its protein kinase and endoribonuclease (RNase) domains. We investigate how binding of cofactors to the kinase domain of Ire1 modulates its RNase activity. RESULTS: Our results suggest that the kinase domain of Ire1 initially binds cofactors without activation of the RNase domain. The RNase is activated upon a subsequent conformational rearrangement of Ire1 governed by the chemical properties of bound cofactors. The conformational step can be selectively inhibited by chemical perturbations of cofactors. Substitution of a single oxygen atom in the terminal beta-phosphate group of a potent cofactor ADP by sulfur results in ADPbetaS, a cofactor that binds to Ire1 as well as ADP, but does not activate the RNase. The RNase activity can be rescued by thiophilic metal ions, such as Mn2+ and Cd2+, revealing a functional metal ion-phosphate interaction, which controls the conformation and the RNase activity of Ire1 * ADP complex. Mutagenesis of the kinase domain suggests that this rearrangement involves movement of the C-helix, generally conserved among protein kinases. Using X-ray crystallography we show that oligomerization of Ire1 is sufficient for placing the alpha C-helix in the active, cofactor-bound-like conformation, even in the absence of cofactors. CONCLUSIONS: Our structural and biochemical evidence converges on a model that the co-factor-induced conformational change in Ire1 is coupled to oligomerization of the receptor, which, in turn, activates the RNase. The data reveal that cofactor-Ire1 interactions occur in two independent steps: binding of a cofactor to Ire1 and subsequent rearrangement of Ire1 resulting in its self-association. The pronounced allosteric effect of cofactors on protein-protein interactions involving Ire1's kinase domain suggests that protein kinases and pseudokinases encoded in metazoan genomes may use ATP pocket binding ligands similarly to exert signaling roles other than phosphoryl-transfer.

Cofactor-mediated conformational control in the bifunctional kinase/RNase Ire1.,Korennykh AV, Egea PF, Korostelev AA, Finer-Moore J, Stroud RM, Zhang C, Shokat KM, Walter P BMC Biol. 2011 Jul 6;9(1):48. PMID:21729334<ref>PMID:21729334</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3sdm" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ire1|Ire1]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Baker's yeast]]
[[Category: Egea, P]]
[[Category: Finer-Moore, J]]
[[Category: Korennykh, A]]
[[Category: Korostelev, A]]
[[Category: Shokat, K]]
[[Category: Stroud, R]]
[[Category: Walter, P]]
[[Category: Zhang, C]]
[[Category: Complex]]
[[Category: Hac1]]
[[Category: Hydrolase]]
[[Category: Kinase]]
[[Category: Oligomer]]
[[Category: Oligonucleotide]]
[[Category: Ribonuclease]]
[[Category: Rna]]
[[Category: Rnase]]
[[Category: Splicing]]
[[Category: Transferase]]
[[Category: Unfolded protein response]]
[[Category: Upr]]
[[Category: Xbp1]]