5VJ2

Structure of human respiratory syncytial virus non-structural protein 1 (NS1)

5VJ2 の概要

• エントリーDOI: 10.2210/pdb5vj2/pdb
• 分子名称: Non-structural protein 1, 1,4-DIETHYLENE DIOXIDE, CHLORIDE ION, ... (5 entities in total)
• 機能のキーワード: rsv, immune modulator, viral protein
• 由来する生物種: Respiratory syncytial virus type A
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 32318.96

構造登録者

Leung, D.W.,Borek, D.M.,Amarasinghe, G.K. (登録日: 2017-04-18, 公開日: 2017-07-12, 最終更新日: 2024-03-13)

主引用文献

Chatterjee, S.,Luthra, P.,Esaulova, E.,Agapov, E.,Yen, B.C.,Borek, D.M.,Edwards, M.R.,Mittal, A.,Jordan, D.S.,Ramanan, P.,Moore, M.L.,Pappu, R.V.,Holtzman, M.J.,Artyomov, M.N.,Basler, C.F.,Amarasinghe, G.K.,Leung, D.W.
Structural basis for human respiratory syncytial virus NS1-mediated modulation of host responses.
Nat Microbiol, 2:17101-17101, 2017

PubMed Abstract: Human respiratory syncytial virus (hRSV) is a major cause of morbidity and mortality in the paediatric, elderly and immune-compromised populations. A gap in our understanding of hRSV disease pathology is the interplay between virally encoded immune antagonists and host components that limit hRSV replication. hRSV encodes for non-structural (NS) proteins that are important immune antagonists; however, the role of these proteins in viral pathogenesis is incompletely understood. Here, we report the crystal structure of hRSV NS1 protein, which suggests that NS1 is a structural paralogue of hRSV matrix (M) protein. Comparative analysis of the shared structural fold with M revealed regions unique to NS1. Studies on NS1 wild type or mutant alone or in recombinant RSVs demonstrate that structural regions unique to NS1 contribute to modulation of host responses, including inhibition of type I interferon responses, suppression of dendritic cell maturation and promotion of inflammatory responses. Transcriptional profiles of A549 cells infected with recombinant RSVs show significant differences in multiple host pathways, suggesting that NS1 may have a greater role in regulating host responses than previously appreciated. These results provide a framework to target NS1 for therapeutic development to limit hRSV-associated morbidity and mortality.

PubMed: 28665409
DOI: 10.1038/nmicrobiol.2017.101

実験手法

X-RAY DIFFRACTION (2.22 Å)