9CCV

Crystal structure of human respiratory syncytial virus NS1 bound to human MED25 ACID

9CCV の概要

• エントリーDOI: 10.2210/pdb9ccv/pdb
• 分子名称: Non-structural protein 1, Mediator of RNA polymerase II transcription subunit 25 (3 entities in total)
• 機能のキーワード: complex, viral protein, host nuclear protein
• 由来する生物種: Human respiratory syncytial virus A; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 36747.46

構造登録者

Kalita, P.,Borek, D.M.,Amarasinghe, G.K.,Leung, D.W. (登録日: 2024-06-23, 公開日: 2025-04-09)

主引用文献

Kalita, P.,Khatavkar, O.,Uwase, G.,Korshunova, Y.,Hu, Y.,Wagner, N.D.,Xu, J.,Pan, J.,Nix, J.C.,Gross, M.L.,Brody, S.L.,Borek, D.,Amarasinghe, G.K.,Payton, J.E.,Leung, D.W.
Molecular basis for human respiratory syncytial virus transcriptional regulator NS1 interactions with MED25.
Nat Commun, 16:2883-2883, 2025

PubMed Abstract: The Mediator complex facilitates interactions between transcription factors and RNA polymerase II, a process that is required for host gene transcription, including in response to viral infections. Among the many subunits in the Mediator complex, the MED25 subunit has been shown to be a target for viral activators during infection. Here we provide the molecular basis for the interaction between human respiratory syncytial virus (hRSV) nonstructural 1 protein (NS1) and the activator interaction domain (ACID) of MED25. The X-ray crystal structure of the complex revealed that NS1 straddles and binds two faces of MED25 ACID. This interaction is distinct from previously known viral activators. Importantly, our data support the conformational flexibility of viral transcriptional regulators. Furthermore, ChIP-seq and RNA-seq analysis identified the ATF3 transcription factor and a role for NS1/Mediator/ATF3 interaction in host gene regulation in hRSV infections. Our findings provide a molecular basis for hRSV NS1-based regulation of host gene transcription and reveal how viruses exploit the conformational heterogeneity at fuzzy transcription activator interfaces.

PubMed: 40128225
DOI: 10.1038/s41467-025-58216-4

実験手法

X-RAY DIFFRACTION (2.53 Å)