6C5V

An anti-gH/gL antibody that neutralizes dual-tropic infection defines a site of vulnerability on Epstein-Barr virus

6C5V の概要

• エントリーDOI: 10.2210/pdb6c5v/pdb
• EMDBエントリー: 7344 7345
• 分子名称: Envelope glycoprotein H, Envelope glycoprotein L, Glycoprotein 42, ... (7 entities in total)
• 機能のキーワード: epstein-barr virus, neutralizing antibodies, gh/gl, glycoproteins, structural genomics, seattle structural genomics center for infectious disease, ssgcid, viral protein
• 由来する生物種: Human herpesvirus 4 (HHV-4); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 167514.83

構造登録者

Snijder, J.,Ortego, M.S.,Weidle, C.,Stuart, A.B.,Gray, M.A.,McElrath, M.J.,Pancera, M.,Veesler, D.,McGuire, A.T.,Seattle Structural Genomics Center for Infectious Disease (SSGCID) (登録日: 2018-01-16, 公開日: 2018-05-02, 最終更新日: 2024-11-06)

主引用文献

Snijder, J.,Ortego, M.S.,Weidle, C.,Stuart, A.B.,Gray, M.D.,McElrath, M.J.,Pancera, M.,Veesler, D.,McGuire, A.T.
An Antibody Targeting the Fusion Machinery Neutralizes Dual-Tropic Infection and Defines a Site of Vulnerability on Epstein-Barr Virus.
Immunity, 48:799-811.e9, 2018

PubMed Abstract: Epstein-Barr virus (EBV) is a causative agent of infectious mononucleosis and is associated with 200,000 new cases of cancer and 140,000 deaths annually. Subunit vaccines against this pathogen have focused on the gp350 glycoprotein and remain unsuccessful. We isolated human antibodies recognizing the EBV fusion machinery (gH/gL and gB) from rare memory B cells. One anti-gH/gL antibody, AMMO1, potently neutralized infection of B cells and epithelial cells, the two major cell types targeted by EBV. We determined a cryo-electron microscopy reconstruction of the gH/gL-gp42-AMMO1 complex and demonstrated that AMMO1 bound to a discontinuous epitope formed by both gH and gL at the Domain-I/Domain-II interface. Integrating structural, biochemical, and infectivity data, we propose that AMMO1 inhibits fusion of the viral and cellular membranes. This work identifies a crucial epitope that may aid in the design of next-generation subunit vaccines against this major public health burden.

PubMed: 29669253
DOI: 10.1016/j.immuni.2018.03.026

実験手法

ELECTRON MICROSCOPY (4.8 Å)