View source for 9vfx


==SARS-CoV-2 spike di-trimer of RBD and NTD==
<StructureSection load='9vfx' size='340' side='right'caption='[[9vfx]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9vfx]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9VFX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9VFX 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]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=9vfx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9vfx OCA], [https://pdbe.org/9vfx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9vfx RCSB], [https://www.ebi.ac.uk/pdbsum/9vfx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9vfx ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SPIKE_SARS2 SPIKE_SARS2] attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Binding to human ACE2 receptor and internalization of the virus into the endosomes of the host cell induces conformational changes in the Spike glycoprotein (PubMed:32142651, PubMed:32075877, PubMed:32155444). Uses also human TMPRSS2 for priming in human lung cells which is an essential step for viral entry (PubMed:32142651). Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membranes fusion within endosomes.[HAMAP-Rule:MF_04099]<ref>PMID:32075877</ref> <ref>PMID:32142651</ref> <ref>PMID:32155444</ref>   mediates fusion of the virion and cellular membranes by acting as a class I viral fusion protein. Under the current model, the protein has at least three conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes.[HAMAP-Rule:MF_04099]  Acts as a viral fusion peptide which is unmasked following S2 cleavage occurring upon virus endocytosis.[HAMAP-Rule:MF_04099]
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== Publication Abstract from PubMed ==
SARS-CoV-2 primarily targets epithelial cells in the respiratory and intestinal tracts where its cognate receptor ACE2 and obligate processing enzymes furin and TMPRSS2 are richly expressed. However, compared with severe inflammation and tissue damage in the lungs of a COVID-19 patient, clinical lesions in the intestine are rare, suggesting an effective intestinal mucosal immunity against SARS-CoV-2 infection. Here, we report that MMP7(-/-)/hACE2 hybrid mice lacking mature enteric alpha-defensins or cryptdins were more susceptible to SARS-CoV-2 infection in the intestine than K18-hACE2 transgenic mice. The mouse alpha-defensin cryptdin-5 (Crp5) displayed potent and broad antiviral activity in vitro and in vivo by two distinct mechanisms, (1) directly targeting the RBD of the spike (S) protein to antagonize its interactions with ACE2, thus blocking viral attachment, membrane fusion and cell-to-cell transmission, and (2) binding to the 630 loop of the S protein to induce its multimerization, thereby impairing proteolytic processing, membrane fusion and, ultimately, viral infectivity. Our findings imply that enteric alpha-defensins help alleviate, as host protective factors, Covid-19 symptoms in the intestine despite higher ACE2 expression in the gut than in the lungs, and that Crp5 may be developed as a broad-spectrum antiviral for the treatment of coronavirus infection irrespective of virus type and variant.

Enteric alpha-defensins contribute to intestinal mucosal immunity against SARS-CoV-2 infection.,Yang Y, Yang Q, Huang X, Liao C, Chen Z, Lu W Mucosal Immunol. 2026 Aug 1:100392. doi: 10.1016/j.mucimm.2026.100392. PMID:42542248<ref>PMID:42542248</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9vfx" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Severe acute respiratory syndrome coronavirus 2]]
[[Category: Yang QX]]
[[Category: Yang YL]]