8FEL

Langya Virus Fusion Protein (LayV-F) in Post-Fusion Conformation

8FEL の概要

• エントリーDOI: 10.2210/pdb8fel/pdb
• EMDBエントリー: 29029 29032
• 分子名称: Fusion Protein (1 entity in total)
• 機能のキーワード: glycoprotein, fusion, paramyxovirus, henipavirus, viral protein
• 由来する生物種: Langya virus
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 177077.31

構造登録者

May, A.J.,Pothula, K.R.,Janowska, K.,Acharya, P. (登録日: 2022-12-06, 公開日: 2023-04-19, 最終更新日: 2024-11-20)

主引用文献

May, A.J.,Pothula, K.R.,Janowska, K.,Acharya, P.
Structures of Langya Virus Fusion Protein Ectodomain in Pre- and Postfusion Conformation.
J.Virol., 97:e0043323-e0043323, 2023

PubMed Abstract: Langya virus (LayV) is a paramyxovirus in the genus, closely related to the deadly Nipah (NiV) and Hendra (HeV) viruses, that was identified in August 2022 through disease surveillance following animal exposure in eastern China. Paramyxoviruses present two glycoproteins on their surface, known as attachment and fusion proteins, that mediate entry into cells and constitute the primary antigenic targets for immune response. Here, we determine cryo-electron microscopy (cryo-EM) structures of the uncleaved LayV fusion protein (F) ectodomain in pre- and postfusion conformations. The LayV-F protein exhibits pre- and postfusion architectures that, despite being highly conserved across paramyxoviruses, show differences in their surface properties, in particular at the apex of the prefusion trimer, that may contribute to antigenic variability. While dramatic conformational changes were visualized between the pre- and postfusion forms of the LayV-F protein, several domains remained invariant, held together by highly conserved disulfides. The LayV-F fusion peptide (FP) is buried within a highly conserved, hydrophobic interprotomer pocket in the prefusion state and is notably less flexible than the rest of the protein, highlighting its "spring-loaded" state and suggesting that the mechanism of pre-to-post transition must involve perturbations to the pocket and release of the fusion peptide. Together, these results offer a structural basis for how the Langya virus fusion protein compares to its Henipavirus relatives and propose a mechanism for the initial step of pre- to postfusion conversion that may apply more broadly to paramyxoviruses. The genus is quickly expanding into new animal hosts and geographic locations. This study compares the structure and antigenicity of the Langya virus fusion protein to other henipaviruses, which have important vaccine and therapeutic development implications. Furthermore, the study proposes a new mechanism to explain the early steps of the fusion initiation process that can be more broadly applied to the family.

PubMed: 37278642
DOI: 10.1128/jvi.00433-23

実験手法

ELECTRON MICROSCOPY (4.64 Å)