7LVU

Structure of RSV F-directed VHH Cl184

7LVU の概要

• エントリーDOI: 10.2210/pdb7lvu/pdb
• 分子名称: F-VHH-Cl184 (2 entities in total)
• 機能のキーワード: nanobody, vhh, antibody, immune system
• 由来する生物種: Lama glama
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 67603.70

構造登録者

Hsieh, C.-L.,McLellan, J.S. (登録日: 2021-02-26, 公開日: 2021-03-24, 最終更新日: 2024-10-30)

主引用文献

Rossey, I.,Hsieh, C.L.,Sedeyn, K.,Ballegeer, M.,Schepens, B.,Mclellan, J.S.,Saelens, X.
A vulnerable, membrane-proximal site in human respiratory syncytial virus F revealed by a prefusion-specific single-domain antibody.
J.Virol., 95:-, 2021

PubMed Abstract: Human respiratory syncytial virus (RSV) is a major cause of lower respiratory tract disease, especially in young children and the elderly. The fusion protein (F) exists in a pre- and postfusion conformation and is the main target of RSV-neutralizing antibodies. Highly potent RSV-neutralizing antibodies typically bind sites that are unique to the prefusion conformation of F. In this study we screened a single-domain antibody (VHH) library derived from a llama immunized with prefusion-stabilized F and identified a prefusion F-specific VHH that can neutralize RSV A at subnanomolar concentrations. Structural analysis revealed that this VHH primarily binds to antigenic site I while also making contacts with residues in antigenic site III and IV. This new VHH reveals a previously underappreciated membrane-proximal region sensitive for neutralization.RSV is an important respiratory pathogen. This study describes a prefusion F-specific VHH that primarily binds to antigenic site I of RSV F. This is the first time that a prefusion F-specific antibody that binds this site is reported. In general, antibodies that bind to site I are poorly neutralizing, whereas the VHH described here neutralizes RSV A at subnanomolar concentrations. Our findings contribute to insights into the RSV F antigenic map.

PubMed: 33692208
DOI: 10.1128/JVI.02279-20

実験手法

X-RAY DIFFRACTION (1.94 Å)