5TP3

Crystal structure of the RSV-neutralizing single-domain antibody F-VHH-4

5TP3 の概要

• エントリーDOI: 10.2210/pdb5tp3/pdb
• 分子名称: F-VHH-4 (2 entities in total)
• 機能のキーワード: nanobody, respiratory syncytial virus, ig fold, fusion glycoprotein, pseudomerohedral, immune system
• 由来する生物種: Lama glama (llama)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 27216.16

構造登録者

Wrapp, D.,Gilman, M.S.A.,McLellan, J.S. (登録日: 2016-10-19, 公開日: 2017-02-22, 最終更新日: 2024-10-16)

主引用文献

Rossey, I.,Gilman, M.S.,Kabeche, S.C.,Sedeyn, K.,Wrapp, D.,Kanekiyo, M.,Chen, M.,Mas, V.,Spitaels, J.,Melero, J.A.,Graham, B.S.,Schepens, B.,McLellan, J.S.,Saelens, X.
Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state.
Nat Commun, 8:14158-14158, 2017

PubMed Abstract: Human respiratory syncytial virus (RSV) is the main cause of lower respiratory tract infections in young children. The RSV fusion protein (F) is highly conserved and is the only viral membrane protein that is essential for infection. The prefusion conformation of RSV F is considered the most relevant target for antiviral strategies because it is the fusion-competent form of the protein and the primary target of neutralizing activity present in human serum. Here, we describe two llama-derived single-domain antibodies (VHHs) that have potent RSV-neutralizing activity and bind selectively to prefusion RSV F with picomolar affinity. Crystal structures of these VHHs in complex with prefusion F show that they recognize a conserved cavity formed by two F protomers. In addition, the VHHs prevent RSV replication and lung infiltration of inflammatory monocytes and T cells in RSV-challenged mice. These prefusion F-specific VHHs represent promising antiviral agents against RSV.

PubMed: 28194013
DOI: 10.1038/ncomms14158

実験手法

X-RAY DIFFRACTION (1.874 Å)