7v0p | pdb_00007v0p

Cryo-EM structure of SINV/EEEV in complex with Fab fragment of a potently neutralizing human antibody IgG-106

spinqualitylabelsall models 7v0p, resolution 5.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7v0p is a 16 chain structure with sequence from Eastern equine encephalitis virus and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 5.2Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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