View source for 7mtd


==Structure of aged SARS-CoV-2 S2P spike at pH 7.4==
<StructureSection load='7mtd' size='340' side='right'caption='[[7mtd]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MTD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MTD 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]] 3.5&#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=7mtd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mtd OCA], [https://pdbe.org/7mtd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mtd RCSB], [https://www.ebi.ac.uk/pdbsum/7mtd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mtd ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The SARS-CoV-2 spike is the primary target of virus-neutralizing antibodies and critical to the development of effective vaccines against COVID-19. Here, we demonstrate that the prefusion-stabilized two-proline "S2P" spike -widely employed for laboratory work and clinical studies- unfolds when stored at 4 degrees C, physiological pH, as observed by electron microscopy (EM) and differential scanning calorimetry, but that its trimeric, native-like conformation can be reacquired by low pH treatment. When stored for approximately one week, this unfolding does not significantly alter antigenic characteristics; however, longer storage diminishes antibody binding, and month-old spike elicits virtually no neutralization in mice despite inducing high ELISA-binding titers. Cryo-EM structures reveal the folded fraction of spike to decrease with aging, though its structure remains largely similar, although with varying mobility of the receptor-binding domain. Thus, the SARS-CoV-2 spike is susceptible to unfolding which affects immunogenicity, highlighting the need to monitor its integrity.

SARS-CoV-2 S2P spike ages through distinct states with altered immunogenicity.,Olia AS, Tsybovsky Y, Chen SJ, Liu C, Nazzari AF, Ou L, Wang L, Kong WP, Leung K, Liu T, Stephens T, Teng IT, Wang S, Yang ES, Zhang B, Zhang Y, Zhou T, Mascola JR, Kwong PD J Biol Chem. 2021 Aug 27:101127. doi: 10.1016/j.jbc.2021.101127. PMID:34461095<ref>PMID:34461095</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7mtd" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Kwong PD]]
[[Category: Olia AS]]
[[Category: Tsybovsky Y]]