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==Crystal structures reveal transient PERK luminal domain tetramerization in ER stress signaling==
<StructureSection load='4yzy' size='340' side='right'caption='[[4yzy]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4yzy]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YZY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YZY FirstGlance]. <br>
</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4yzy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yzy OCA], [https://pdbe.org/4yzy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yzy RCSB], [https://www.ebi.ac.uk/pdbsum/4yzy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yzy ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/E2AK3_MOUSE E2AK3_MOUSE] Phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2 (EIF2), leading to its inactivation and thus to a rapid reduction of translational initiation and repression of global protein synthesis. Serves as a critical effector of unfolded protein response (UPR)-induced G1 growth arrest due to the loss of cyclin-D1 (CCND1).<ref>PMID:11035797</ref> 
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== Publication Abstract from PubMed ==
Stress caused by accumulation of misfolded proteins within the endoplasmic reticulum (ER) elicits a cellular unfolded protein response (UPR) aimed at maintaining protein-folding capacity. PERK, a key upstream component, recognizes ER stress via its luminal sensor/transducer domain, but the molecular events that lead to UPR activation remain unclear. Here, we describe the crystal structures of mammalian PERK luminal domains captured in dimeric state as well as in a novel tetrameric state. Small angle X-ray scattering analysis (SAXS) supports the existence of both crystal structures also in solution. The salient feature of the tetramer interface, a helix swapped between dimers, implies transient association. Moreover, interface mutations that disrupt tetramer formation in vitro reduce phosphorylation of PERK and its target eIF2alpha in cells. These results suggest that transient conversion from dimeric to tetrameric state may be a key regulatory step in UPR activation.

Crystal structures reveal transient PERK luminal domain tetramerization in endoplasmic reticulum stress signaling.,Carrara M, Prischi F, Nowak PR, Ali MM EMBO J. 2015 Apr 28. pii: e201489183. PMID:25925385<ref>PMID:25925385</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 4yzy" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Ali MMU]]
[[Category: Carrara M]]
[[Category: Prischi F]]