8XK6

S2A5 Fab bound to SFTSV glycoprotein Gn

8XK6 の概要

• エントリーDOI: 10.2210/pdb8xk6/pdb
• 分子名称: Envelopment polyprotein, mAb S2A5 Fab heavy chain, mAb S2A5 Fab light chain, ... (4 entities in total)
• 機能のキーワード: glycoprotein, gn, fab, viral protein
• 由来する生物種: Severe fever with thrombocytopenia syndrome virus; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 92220.66

構造登録者

Deng, Z. (登録日: 2023-12-22, 公開日: 2024-07-10, 最終更新日: 2024-11-20)

主引用文献

Ren, X.,Sun, J.,Kuang, W.,Yu, F.,Wang, B.,Wang, Y.,Deng, W.,Xu, Z.,Yang, S.,Wang, H.,Hu, Y.,Deng, Z.,Ning, Y.J.,Zhao, H.
A broadly protective antibody targeting glycoprotein Gn inhibits severe fever with thrombocytopenia syndrome virus infection.
Nat Commun, 15:7009-7009, 2024

PubMed Abstract: Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging bunyavirus that causes severe viral hemorrhagic fever and thrombocytopenia syndrome with a fatality rate of up to 30%. No licensed vaccines or therapeutics are currently available for humans. Here, we develop seven monoclonal antibodies (mAbs) against SFTSV surface glycoprotein Gn. Mechanistic studies show that three neutralizing mAbs (S2A5, S1G3, and S1H7) block multiple steps during SFTSV infection, including viral attachment and membrane fusion, whereas another neutralizing mAb (B1G11) primarily inhibits the viral attachment step. Epitope binning and X-ray crystallographic analyses reveal four distinct antigenic sites on Gn, three of which have not previously been reported, corresponding to domain I, domain II, and spanning domain I and domain II. One of the most potent neutralizing mAbs, S2A5, binds to a conserved epitope on Gn domain I and broadly neutralizes infection of six SFTSV strains corresponding to genotypes A to F. A single dose treatment of S2A5 affords both pre- and post-exposure protection of mice against lethal SFTSV challenge without apparent weight loss. Our results support the importance of glycoprotein Gn for eliciting a robust humoral response and pave a path for developing prophylactic and therapeutic antibodies against SFTSV infection.

PubMed: 39147753
DOI: 10.1038/s41467-024-51108-z

実験手法

X-RAY DIFFRACTION (2.45 Å)