8V5K

Structure of the Human Respirovirus 3 Fusion Protein Bound to Camelid Nanobodies 4C03 and 4C06

8V5K の概要

• エントリーDOI: 10.2210/pdb8v5k/pdb
• EMDBエントリー: 42983
• 分子名称: Fusion glycoprotein F0, Camelid Nanobody 4C03, Camelid Nanobody 4C06, ... (4 entities in total)
• 機能のキーワード: viral fusion protein, camelid nanobodies, viral glycoprotein, membrane fusion, viral protein, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Human respirovirus 3; 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 245401.09

構造登録者

Johnson, N.V.,Ramamohan, A.R.,McLellan, J.S. (登録日: 2023-11-30, 公開日: 2024-05-22, 最終更新日: 2024-10-30)

主引用文献

Johnson, N.V.,van Scherpenzeel, R.C.,Bakkers, M.J.G.,Ramamohan, A.R.,van Overveld, D.,Le, L.,Langedijk, J.P.M.,Kolkman, J.A.,McLellan, J.S.
Structural basis for potent neutralization of human respirovirus type 3 by protective single-domain camelid antibodies.
Nat Commun, 15:5458-5458, 2024

PubMed Abstract: Respirovirus 3 is a leading cause of severe acute respiratory infections in vulnerable human populations. Entry into host cells is facilitated by the attachment glycoprotein and the fusion glycoprotein (F). Because of its crucial role, F represents an attractive therapeutic target. Here, we identify 13 F-directed heavy-chain-only antibody fragments that neutralize recombinant respirovirus 3. High-resolution cryo-EM structures of antibody fragments bound to the prefusion conformation of F reveal three distinct, previously uncharacterized epitopes. All three antibody fragments bind quaternary epitopes on F, suggesting mechanisms for neutralization that may include stabilization of the prefusion conformation. Studies in cotton rats demonstrate the prophylactic efficacy of these antibody fragments in reducing viral load in the lungs and nasal passages. These data highlight the potential of heavy-chain-only antibody fragments as effective interventions against respirovirus 3 infection and identify neutralizing epitopes that can be targeted for therapeutic development.

PubMed: 38937429
DOI: 10.1038/s41467-024-49757-1

実験手法

ELECTRON MICROSCOPY (2.6 Å)