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| | <StructureSection load='4yzy' size='340' side='right'caption='[[4yzy]], [[Resolution|resolution]] 3.20Å' scene=''> | | <StructureSection load='4yzy' size='340' side='right'caption='[[4yzy]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4yzy]] is a 1 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YZY FirstGlance]. <br> | + | <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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></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]] 3.2Å</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=4yzy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yzy OCA], [http://pdbe.org/4yzy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yzy RCSB], [http://www.ebi.ac.uk/pdbsum/4yzy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4yzy ProSAT]</span></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> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Non-specific serine/threonine protein kinase]] | + | [[Category: Mus musculus]] |
| - | [[Category: Ali, M M.U]] | + | [[Category: Ali MMU]] |
| - | [[Category: Carrara, M]] | + | [[Category: Carrara M]] |
| - | [[Category: Prischi, F]] | + | [[Category: Prischi F]] |
| - | [[Category: Dimer]]
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| - | [[Category: Er stress sensing]]
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| - | [[Category: Perk]]
| + | |
| - | [[Category: Proteostasis]]
| + | |
| - | [[Category: Signaling protein]]
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| - | [[Category: Upr]]
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| Structural highlights
Function
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).[1]
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Brewer JW, Diehl JA. PERK mediates cell-cycle exit during the mammalian unfolded protein response. Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12625-30. PMID:11035797 doi:http://dx.doi.org/10.1073/pnas.220247197
- ↑ Carrara M, Prischi F, Nowak PR, Ali MM. Crystal structures reveal transient PERK luminal domain tetramerization in endoplasmic reticulum stress signaling. EMBO J. 2015 Apr 28. pii: e201489183. PMID:25925385 doi:http://dx.doi.org/10.15252/embj.201489183
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