6GV4

High-resolution Cryo-EM of Fab-labeled human parechovirus 3

6GV4 の概要

• エントリーDOI: 10.2210/pdb6gv4/pdb
• EMDBエントリー: 0069
• 分子名称: RNA (5'-R(*UP*GP*GP*UP*AP*UP*UP*U)-3'), VP0, VP1, ... (6 entities in total)
• 機能のキーワード: human parechovirus, antibody, rna, virus
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 114414.67

構造登録者

Domanska, A.,Flatt, J.W.,Jukonen, J.J.J.,Geraets, J.A.,Butcher, S.J. (登録日: 2018-06-20, 公開日: 2018-11-21, 最終更新日: 2024-11-06)

主引用文献

Domanska, A.,Flatt, J.W.,Jukonen, J.J.J.,Geraets, J.A.,Butcher, S.J.
A 2.8-Angstrom-Resolution Cryo-Electron Microscopy Structure of Human Parechovirus 3 in Complex with Fab from a Neutralizing Antibody.
J.Virol., 93:-, 2019

PubMed Abstract: Human parechovirus 3 (HPeV3) infection is associated with sepsis characterized by significant immune activation and subsequent tissue damage in neonates. Strategies to limit infection have been unsuccessful due to inadequate molecular diagnostic tools for early detection and the lack of a vaccine or specific antiviral therapy. Toward the latter, we present a 2.8-Å-resolution structure of HPeV3 in complex with fragments from a neutralizing human monoclonal antibody, AT12-015, using cryo-electron microscopy (cryo-EM) and image reconstruction. Modeling revealed that the epitope extends across neighboring asymmetric units with contributions from capsid proteins VP0, VP1, and VP3. Antibody decoration was found to block binding of HPeV3 to cultured cells. Additionally, at high resolution, it was possible to model a stretch of RNA inside the virion and, from this, identify the key features that drive and stabilize protein-RNA association during assembly. Human parechovirus 3 (HPeV3) is receiving increasing attention as a prevalent cause of sepsis-like symptoms in neonates, for which, despite the severity of disease, there are no effective treatments available. Structural and molecular insights into virus neutralization are urgently needed, especially as clinical cases are on the rise. Toward this goal, we present the first structure of HPeV3 in complex with fragments from a neutralizing monoclonal antibody. At high resolution, it was possible to precisely define the epitope that, when targeted, prevents virions from binding to cells. Such an atomic-level description is useful for understanding host-pathogen interactions and viral pathogenesis mechanisms and for finding potential cures for infection and disease.

PubMed: 30463974
DOI: 10.1128/JVI.01597-18

実験手法

ELECTRON MICROSCOPY (2.8 Å)