8VSV

Cryo-EM structure of SINV/EEEV in complex with a potently neutralizing intact human antibody EEEV-373

8VSV の概要

• エントリーDOI: 10.2210/pdb8vsv/pdb
• EMDBエントリー: 43507
• 分子名称: IgG EEEV-373 Heavy chain, IgG EEEV-373 Light chain., Spike glycoprotein E1, ... (6 entities in total)
• 機能のキーワード: cryo-em, single particle averaging, virus neutralization, intact human antibody, quaternary epitope, intra-virion crosslink, virus-immune system complex., virus
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 589507.70

構造登録者

Bandyopadhyay, A.,Klose, T.,Kuhn, R.J. (登録日: 2024-01-24, 公開日: 2025-06-11, 最終更新日: 2025-12-24)

主引用文献

Bandyopadhyay, A.,Williamson, L.E.,Sirohi, D.,Bailey, K.,Gilliland Jr., T.,Klose, T.,Buda, G.,Trivette, A.,Sun, C.,Julander, J.G.,Klimstra, W.B.,Crowe Jr., J.E.,Kuhn, R.J.
Structural elucidation of a unique binding mode by an intact alphavirus human IgG molecule to a quaternary epitope.
Nat Commun, 16:7716-7716, 2025

PubMed Abstract: Eastern equine encephalitis virus (EEEV) is a mosquito-transmitted alphavirus that can cause severe encephalitis in humans and horses with a high case fatality rate. There are no licensed EEEV vaccines or therapeutics for human use, warranting the need to better understand the human immune response against EEEV. Here we present a cryo-EM reconstruction of the chimeric virus, Sindbis (SINV)/EEEV, in complex with a potently neutralizing and efficacious intact human IgG1 antibody in a mouse model of infection and disease. This antibody requires bivalency to recognize a quaternary epitope on the E2 glycoprotein and cross-links two virus spikes across the icosahedral two-fold axis through a unique binding mode. Kinetic analysis of the binding interaction provides insights into this distinguishing feature. Mechanistically, the antibody inhibits viral entry into cells through blockade of receptor binding and early fusion events but does not block egress, thereby, exclusively targeting an epitope found on intact virions. The discovery of the quaternary epitope and unique binding mode recognized by this antibody together advance our understanding of the complexity of antibody-antigen interactions and can aid in vaccine design to elicit recognition of distinct epitopes of clinically relevant alphaviruses.

PubMed: 40830099
DOI: 10.1038/s41467-025-60505-x

実験手法

ELECTRON MICROSCOPY (3.8 Å)