8Y3U

Ebola virus glycoprotein in complex with a broadly neutralizing antibody 2G1

8Y3U の概要

• エントリーDOI: 10.2210/pdb8y3u/pdb
• EMDBエントリー: 38899
• 分子名称: 2G1 VH, 2G1 VL, Virion spike glycoprotein, ... (5 entities in total)
• 機能のキーワード: antiviral protein
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 160968.36

構造登録者

Fan, P.F.,Yu, C.M.,Chen, W. (登録日: 2024-01-29, 公開日: 2024-08-07, 最終更新日: 2025-02-19)

主引用文献

Fan, P.,Sun, B.,Liu, Z.,Fang, T.,Ren, Y.,Zhao, X.,Song, Z.,Yang, Y.,Li, J.,Yu, C.,Chen, W.
A pan-orthoebolavirus neutralizing antibody encoded by mRNA effectively prevents virus infection.
Emerg Microbes Infect, 13:2432366-2432366, 2024

PubMed Abstract: is a genus of hazardous pathogens that has caused over 30 outbreaks. However, currently approved therapies are limited in scope, as they are only effective against the Ebola virus and lack cross-protection against other orthoebolaviruses. Here, we demonstrate that a previously isolated human-derived antibody, 2G1, can recognize the glycoprotein (GP) of every orthoebolavirus species. The cryo-electron microscopy structure of 2G1 Fab in complex with the GPΔMucin trimer reveals that 2G1 binds a quaternary pocket formed by three subunits from two GP protomers. 2G1 recognizes highly conserved epitopes among filoviruses and achieves neutralization by blocking GP proteolysis. We designed an efficient mRNA module capable of producing test antibodies at expression levels exceeding 1500 ng/mL in vitro. The lipid nanoparticle (LNP)-encapsulated mRNA-2G1 exhibited potent neutralizing activities against the HIV-pseudotyped Ebola and Sudan viruses that were 19.8 and 12.5 times that of IgG format, respectively. In mice, the antibodies encoded by the mRNA-2G1-LNP peaked within 24 h, effectively blocking the invasion of pseudoviruses with no apparent liver toxicity. This study suggests that the 2G1 antibody and its mRNA formulation represent promising candidate interventions for orthoebolavirus disease, and it provides an efficient mRNA framework applicable to antibody-based therapies.

PubMed: 39560055
DOI: 10.1080/22221751.2024.2432366

実験手法

ELECTRON MICROSCOPY (2.98 Å)