8WSU

Crystal structure of SFTSV Gc and antibody

8WSU の概要

• エントリーDOI: 10.2210/pdb8wsu/pdb
• 分子名称: Glycoprotein C, Ab-H, Ab-L (3 entities in total)
• 機能のキーワード: virus, antibody, viral protein/immune system, viral protein-immune system complex
• 由来する生物種: SFTS phlebovirus (isolate SFTSV/Human/China/HB29/2010) (Severe fever with thrombocytopenia virus); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 188636.17

構造登録者

Chang, Z.,Gao, F.,Wu, Y. (登録日: 2023-10-17, 公開日: 2024-06-12, 最終更新日: 2024-11-06)

主引用文献

Chang, Z.,Gao, D.,Liao, L.,Sun, J.,Zhang, G.,Zhang, X.,Wang, F.,Li, C.,Oladejo, B.O.,Li, S.,Chai, Y.,Hu, Y.,Lu, X.,Xiao, H.,Qi, J.,Chen, Z.,Gao, F.,Wu, Y.
Bispecific antibodies targeting two glycoproteins on SFTSV exhibit synergistic neutralization and protection in a mouse model.
Proc.Natl.Acad.Sci.USA, 121:e2400163121-e2400163121, 2024

PubMed Abstract: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with a high fatality rate of up to 30% caused by SFTS virus (SFTSV). However, no specific vaccine or antiviral therapy has been approved for clinical use. To develop an effective treatment, we isolated a panel of human monoclonal antibodies (mAbs). SF5 and SF83 are two neutralizing mAbs that recognize two viral glycoproteins (Gn and Gc), respectively. We found that their epitopes are closely located, and we then engineered them as several bispecific antibodies (bsAbs). Neutralization and animal experiments indicated that bsAbs display more potent protective effects than the parental mAbs, and the cryoelectron microscopy structure of a bsAb3 Fab-Gn-Gc complex elucidated the mechanism of protection. In vivo virus passage in the presence of antibodies indicated that two bsAbs resulted in less selective pressure and could efficiently bind to all single parental mAb-escape mutants. Furthermore, epitope analysis of the protective mAbs against SFTSV and RVFV indicated that they are all located on the Gn subdomain I, where may be the hot spots in the phleboviruses. Collectively, these data provide potential therapeutic agents and molecular basis for the rational design of vaccines against SFTSV infection.

PubMed: 38830098
DOI: 10.1073/pnas.2400163121

実験手法

X-RAY DIFFRACTION (3.3 Å)