View source for 8hr0


==The complex structure of COPII coat with HCoV-OC43 DD sorting motif==
<StructureSection load='8hr0' size='340' side='right'caption='[[8hr0]], [[Resolution|resolution]] 3.34&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8hr0]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_coronavirus_OC43 Human coronavirus OC43]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8HR0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8HR0 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]] 3.34&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=8hr0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8hr0 OCA], [https://pdbe.org/8hr0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8hr0 RCSB], [https://www.ebi.ac.uk/pdbsum/8hr0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8hr0 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/SC23A_HUMAN SC23A_HUMAN] Defects in SEC23A are the cause of craniolenticulosutural dysplasia (CLSD) [MIM:[https://omim.org/entry/607812 607812]; also known as cranio-lenticulo-sutural dysplasia. CLSD is an autosomal recessive syndrome characterized by late-closing fontanels, sutural cataracts, facial dysmorphisms and skeletal defects.<ref>PMID:16980979</ref> 
== Function ==
[https://www.uniprot.org/uniprot/SC23A_HUMAN SC23A_HUMAN] Component of the COPII coat, that covers ER-derived vesicles involved in transport from the endoplasmic reticulum to the Golgi apparatus. COPII acts in the cytoplasm to promote the transport of secretory, plasma membrane, and vacuolar proteins from the endoplasmic reticulum to the Golgi complex.
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== Publication Abstract from PubMed ==
Via an insufficient coat protein complex I (COPI) retrieval signal, the majority of SARS-CoV-2 spike (S) is resident in host early secretory organelles and a tiny amount is leaked out in cell surface. Only surface-exposed S can be recognized by B cell receptor (BCR) or anti-S therapeutic monoclonal antibodies (mAbs) that is the trigger step for B cell activation after S mRNA vaccination or infected cell clearance by S mAbs. Now, a drug strategy to promote S host surface exposure is absent. Here, we first combined structural and biochemical analysis to characterize S COPI sorting signals. A potent S COPI sorting inhibitor was then invented, evidently capable of promoting S surface exposure and facilitating infected cell clearance by S antibody-dependent cellular cytotoxicity (ADCC). Importantly, with the inhibitor as a probe, we revealed Omicron BA.1 S is less cell surface exposed than prototypes because of a constellation of S folding mutations, possibly corresponding to its ER chaperone association. Our findings not only suggest COPI is a druggable target against COVID-19, but also highlight SARS-CoV-2 evolution mechanism driven by S folding and trafficking mutations.

SARS-CoV-2 spike host cell surface exposure promoted by a COPI sorting inhibitor.,Li Y, Yang M, Nan Y, Wang J, Wang S, Cui D, Guo J, He P, Dai W, Zhou S, Zhang Y, Ma W Acta Pharm Sin B. 2023 Apr 18;13(7):3043-53. doi: 10.1016/j.apsb.2023.04.007. PMID:37360012<ref>PMID:37360012</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8hr0" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Human coronavirus OC43]]
[[Category: Large Structures]]
[[Category: Li YQ]]
[[Category: Ma WF]]
[[Category: Nan YN]]
[[Category: Yang MR]]