7LDK

Structure of human respiratory syncytial virus nonstructural protein 2 (NS2)

7LDK の概要

• エントリーDOI: 10.2210/pdb7ldk/pdb
• 分子名称: Non-structural protein 2, D(-)-TARTARIC ACID, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: nonstructural protein, interferon antagonist, viral protein
• 由来する生物種: Human respiratory syncytial virus A
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 45152.38

構造登録者

Chatterjee, S.,Borek, D.,Otwinowski, Z.,Amarasinghe, G.K.,Leung, D.W. (登録日: 2021-01-13, 公開日: 2021-03-17, 最終更新日: 2024-04-03)

主引用文献

Pei, J.,Wagner, N.D.,Zou, A.J.,Chatterjee, S.,Borek, D.,Cole, A.R.,Kim, P.J.,Basler, C.F.,Otwinowski, Z.,Gross, M.L.,Amarasinghe, G.K.,Leung, D.W.
Structural basis for IFN antagonism by human respiratory syncytial virus nonstructural protein 2.
Proc.Natl.Acad.Sci.USA, 118:-, 2021

PubMed Abstract: Human respiratory syncytial virus (RSV) nonstructural protein 2 (NS2) inhibits host interferon (IFN) responses stimulated by RSV infection by targeting early steps in the IFN-signaling pathway. But the molecular mechanisms related to how NS2 regulates these processes remain incompletely understood. To address this gap, here we solved the X-ray crystal structure of NS2. This structure revealed a unique fold that is distinct from other known viral IFN antagonists, including RSV NS1. We also show that NS2 directly interacts with an inactive conformation of the RIG-I-like receptors (RLRs) RIG-I and MDA5. NS2 binding prevents RLR ubiquitination, a process critical for prolonged activation of downstream signaling. Structural analysis, including by hydrogen-deuterium exchange coupled to mass spectrometry, revealed that the N terminus of NS2 is essential for binding to the RIG-I caspase activation and recruitment domains. N-terminal mutations significantly diminish RIG-I interactions and result in increased IFNβ messenger RNA levels. Collectively, our studies uncover a previously unappreciated regulatory mechanism by which NS2 further modulates host responses and define an approach for targeting host responses.

PubMed: 33649232
DOI: 10.1073/pnas.2020587118

実験手法

X-RAY DIFFRACTION (2.82 Å)