View source for 8zyf


==Crystal structure of ZW2G10 Fab in complex with omicron RBD==
<StructureSection load='8zyf' size='340' side='right'caption='[[8zyf]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8zyf]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [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=8ZYF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ZYF 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]] 2.6&#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=8zyf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8zyf OCA], [https://pdbe.org/8zyf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8zyf RCSB], [https://www.ebi.ac.uk/pdbsum/8zyf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8zyf 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]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its multiple variants continue to spread worldwide, causing respiratory symptoms primarily through mucosal infection. The mucosa serves as the primary barrier against viral entry, in which secretory immunoglobulin A (sIgA) plays a critical role in preventing infection. Here, we engineered and characterized a neutralizing monoclonal antibody, ZW2G10, in IgG, monomeric, dimeric, secretory IgA1, and IgA2 formats. All seven forms of the ZW2G10 antibody showed similar thermal stability. sIgA, especially sIgA1, displayed enhanced neutralizing activity against Omicron-lineage BA.2.75, BA.2.76 and BA.4/5 pseudoviruses compared to IgG. Nasal administration of sIgA1 conferred robust protection against the BA.2.76 pseudovirus in ACE2 transgenic mice, and its protective efficacy was superior to that of IgG. The crystal structure of Omicron receptor binding domain (RBD) and ZW2G10 antibody fragment (Fab) complex revealed that ZW2G10 had no clashes with ACE2. Thus, nasal administration of sIgA may serve as a promising tool for the prevention and treatment of Omicron infection.

Nasal delivery of secretory IgA confers enhanced neutralizing activity against Omicron variants compared to its IgG counterpart.,Zhang G, Huang P, Yuan H, Li E, Chi X, Sun H, Han J, Fang T, Dong Y, Li J, Wang Y, Li J, Chiu S, Yu C Mol Ther. 2025 Mar 1:S1525-0016(25)00166-2. doi: 10.1016/j.ymthe.2025.02.041. PMID:40025736<ref>PMID:40025736</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8zyf" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Severe acute respiratory syndrome coronavirus 2]]
[[Category: Li JM]]
[[Category: Yuan HY]]