7v0p
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Cryo-EM structure of SINV/EEEV in complex with Fab fragment of a potently neutralizing human antibody IgG-106== | |
| + | <StructureSection load='7v0p' size='340' side='right'caption='[[7v0p]], [[Resolution|resolution]] 5.20Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7v0p]] is a 16 chain structure with sequence from [https://en.wikipedia.org/wiki/Eastern_equine_encephalitis_virus Eastern equine encephalitis virus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7V0P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7V0P 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]] 5.2Å</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=7v0p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7v0p OCA], [https://pdbe.org/7v0p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7v0p RCSB], [https://www.ebi.ac.uk/pdbsum/7v0p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7v0p ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Selection and development of monoclonal antibody (mAb) therapeutics against pathogenic viruses depends on certain functional characteristics. Neutralization potency, or the half-maximal inhibitory concentration (IC(50)) values, is an important characteristic of candidate therapeutic antibodies. Structural insights into the bases of neutralization potency differences between antiviral neutralizing mAbs are lacking. In this report, we present cryo-electron microscopy (EM) reconstructions of three anti-Eastern equine encephalitis virus (EEEV) neutralizing human mAbs targeting overlapping epitopes on the E2 protein, with greater than 20-fold differences in their respective IC(50) values. From our structural and biophysical analyses, we identify several constraints that contribute to the observed differences in the neutralization potencies. Cryo-EM reconstructions of EEEV in complex with these Fab fragments reveal structural constraints that dictate intravirion or intervirion cross-linking of glycoprotein spikes by their IgG counterparts as a mechanism of neutralization. Additionally, we describe critical features for the recognition of EEEV by these mAbs including the epitope-paratope interaction surface, occupancy, and kinetic differences in on-rate for binding to the E2 protein. Each constraint contributes to the extent of EEEV inhibition for blockade of virus entry, fusion, and/or egress. These findings provide structural and biophysical insights into the differences in mechanism and neutralization potencies of these antibodies, which help inform rational design principles for candidate vaccines and therapeutic antibodies for all icosahedral viruses. | ||
| - | + | Structural constraints link differences in neutralization potency of human anti-Eastern equine encephalitis virus monoclonal antibodies.,Williamson LE, Bandyopadhyay A, Bailey K, Sirohi D, Klose T, Julander JG, Kuhn RJ, Crowe JE Jr Proc Natl Acad Sci U S A. 2023 Mar 28;120(13):e2213690120. doi: , 10.1073/pnas.2213690120. Epub 2023 Mar 24. PMID:36961925<ref>PMID:36961925</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 7v0p" style="background-color:#fffaf0;"></div> |
| - | [[Category: Klose | + | == References == |
| - | [[Category: | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Eastern equine encephalitis virus]] | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Bandyopadhyay A]] | ||
| + | [[Category: Klose T]] | ||
| + | [[Category: Kuhn RJ]] | ||
Current revision
Cryo-EM structure of SINV/EEEV in complex with Fab fragment of a potently neutralizing human antibody IgG-106
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