View source for 7vlk


==eIF2B-SFSV NSs C2-imposed==
<StructureSection load='7vlk' size='340' side='right'caption='[[7vlk]], [[Resolution|resolution]] 2.27&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7vlk]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Sandfly_fever_Sicilian_virus Sandfly fever Sicilian virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7VLK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VLK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.27&#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=7vlk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vlk OCA], [https://pdbe.org/7vlk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vlk RCSB], [https://www.ebi.ac.uk/pdbsum/7vlk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vlk ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/EI2BA_HUMAN EI2BA_HUMAN] Cree leukoencephalopathy;Late infantile CACH syndrome;Ovarioleukodystrophy. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/EI2BA_HUMAN EI2BA_HUMAN] Catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Various stressors such as viral infection lead to the suppression of cap-dependent translation and the activation of the integrated stress response (ISR), since the stress-induced phosphorylated eukaryotic translation initiation factor 2 [eIF2(alphaP)] tightly binds to eIF2B to prevent it from exchanging guanine nucleotide molecules on its substrate, unphosphorylated eIF2. Sandfly fever Sicilian virus (SFSV) evades this cap-dependent translation suppression through the interaction between its nonstructural protein NSs and host eIF2B. However, its precise mechanism has remained unclear. Here, our cryo-electron microscopy (cryo-EM) analysis reveals that SFSV NSs binds to the alpha-subunit of eIF2B in a competitive manner with eIF2(alphaP). Together with SFSV NSs, eIF2B retains nucleotide exchange activity even in the presence of eIF2(alphaP), in line with the cryo-EM structures of the eIF2B*SFSV NSs*unphosphorylated eIF2 complex. A genome-wide ribosome profiling analysis clarified that SFSV NSs expressed in cultured human cells attenuates the ISR triggered by thapsigargin, an endoplasmic reticulum stress inducer. Furthermore, SFSV NSs introduced in rat hippocampal neurons and human induced-pluripotent stem (iPS) cell-derived motor neurons exhibits neuroprotective effects against the ISR-inducing stress. Since ISR inhibition is beneficial in various neurological disease models, SFSV NSs may be a promising therapeutic ISR inhibitor.

eIF2B-capturing viral protein NSs suppresses the integrated stress response.,Kashiwagi K, Shichino Y, Osaki T, Sakamoto A, Nishimoto M, Takahashi M, Mito M, Weber F, Ikeuchi Y, Iwasaki S, Ito T Nat Commun. 2021 Dec 7;12(1):7102. doi: 10.1038/s41467-021-27337-x. PMID:34876589<ref>PMID:34876589</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7vlk" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Sandfly fever Sicilian virus]]
[[Category: Ito T]]
[[Category: Kashiwagi K]]