8V5A

Prefusion-stabilized Respirovirus type 3 Fusion protein

これはPDB形式変換不可エントリーです。

8V5A の概要

• エントリーDOI: 10.2210/pdb8v5a/pdb
• EMDBエントリー: 42981
• 分子名称: Fusion glycoprotein F0, Camelid nanobody 4C06 (2 entities in total)
• 機能のキーワード: fusion protein, 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: 6
• 化学式量合計: 199907.12

構造登録者

Johnson, N.V.,McLellan, J.S. (登録日: 2023-11-30, 公開日: 2024-06-19, 最終更新日: 2024-11-20)

主引用文献

Langedijk, J.P.M.,Cox, F.,Johnson, N.V.,van Overveld, D.,Le, L.,van den Hoogen, W.,Voorzaat, R.,Zahn, R.,van der Fits, L.,Juraszek, J.,McLellan, J.S.,Bakkers, M.J.G.
Universal paramyxovirus vaccine design by stabilizing regions involved in structural transformation of the fusion protein.
Nat Commun, 15:4629-4629, 2024

PubMed Abstract: The Paramyxoviridae family encompasses medically significant RNA viruses, including human respiroviruses 1 and 3 (RV1, RV3), and zoonotic pathogens like Nipah virus (NiV). RV3, previously known as parainfluenza type 3, for which no vaccines or antivirals have been approved, causes respiratory tract infections in vulnerable populations. The RV3 fusion (F) protein is inherently metastable and will likely require prefusion (preF) stabilization for vaccine effectiveness. Here we used structure-based design to stabilize regions involved in structural transformation to generate a preF protein vaccine antigen with high expression and stability, and which, by stabilizing the coiled-coil stem region, does not require a heterologous trimerization domain. The preF candidate induces strong neutralizing antibody responses in both female naïve and pre-exposed mice and provides protection in a cotton rat challenge model (female). Despite the evolutionary distance of paramyxovirus F proteins, their structural transformation and local regions of instability are conserved, which allows successful transfer of stabilizing substitutions to the distant preF proteins of RV1 and NiV. This work presents a successful vaccine antigen design for RV3 and provides a toolbox for future paramyxovirus vaccine design and pandemic preparedness.

PubMed: 38821950
DOI: 10.1038/s41467-024-48059-w

実験手法

ELECTRON MICROSCOPY (3 Å)