8DEF

Cryo-EM Structure of Western Equine Encephalitis Virus VLP in complex with SKW24 fab

8DEF の概要

• エントリーDOI: 10.2210/pdb8def/pdb
• EMDBエントリー: 27392
• 分子名称: Spike glycoprotein E1, Spike glycoprotein E2, SKW24 Fab heavy chain, ... (4 entities in total)
• 機能のキーワード: western equine encephalitis virus, virus-like particle, antibody, vlp-fab complex, virus-immune system complex, virus/immune system
• 由来する生物種: Western equine encephalitis virus; 詳細
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 377347.89

構造登録者

Pletnev, S.,Tsybovsky, Y.,Verardi, R.,Roedeger, M.,Kwong, P.D. (登録日: 2022-06-20, 公開日: 2023-07-05, 最終更新日: 2024-10-16)

主引用文献

Sutton, M.S.,Pletnev, S.,Callahan, V.,Ko, S.,Tsybovsky, Y.,Bylund, T.,Casner, R.G.,Cerutti, G.,Gardner, C.L.,Guirguis, V.,Verardi, R.,Zhang, B.,Ambrozak, D.,Beddall, M.,Lei, H.,Yang, E.S.,Liu, T.,Henry, A.R.,Rawi, R.,Schon, A.,Schramm, C.A.,Shen, C.H.,Shi, W.,Stephens, T.,Yang, Y.,Florez, M.B.,Ledgerwood, J.E.,Burke, C.W.,Shapiro, L.,Fox, J.M.,Kwong, P.D.,Roederer, M.
Vaccine elicitation and structural basis for antibody protection against alphaviruses.
Cell, 186:2672-2689.e25, 2023

PubMed Abstract: Alphaviruses are RNA viruses that represent emerging public health threats. To identify protective antibodies, we immunized macaques with a mixture of western, eastern, and Venezuelan equine encephalitis virus-like particles (VLPs), a regimen that protects against aerosol challenge with all three viruses. Single- and triple-virus-specific antibodies were isolated, and we identified 21 unique binding groups. Cryo-EM structures revealed that broad VLP binding inversely correlated with sequence and conformational variability. One triple-specific antibody, SKT05, bound proximal to the fusion peptide and neutralized all three Env-pseudotyped encephalitic alphaviruses by using different symmetry elements for recognition across VLPs. Neutralization in other assays (e.g., chimeric Sindbis virus) yielded variable results. SKT05 bound backbone atoms of sequence-diverse residues, enabling broad recognition despite sequence variability; accordingly, SKT05 protected mice against Venezuelan equine encephalitis virus, chikungunya virus, and Ross River virus challenges. Thus, a single vaccine-elicited antibody can protect in vivo against a broad range of alphaviruses.

PubMed: 37295404
DOI: 10.1016/j.cell.2023.05.019

実験手法

ELECTRON MICROSCOPY (4.2 Å)