7LDK
Structure of human respiratory syncytial virus nonstructural protein 2 (NS2)
Summary for 7LDK
| Entry DOI | 10.2210/pdb7ldk/pdb |
| Descriptor | Non-structural protein 2, D(-)-TARTARIC ACID, CHLORIDE ION, ... (4 entities in total) |
| Functional Keywords | nonstructural protein, interferon antagonist, viral protein |
| Biological source | Human respiratory syncytial virus A |
| Total number of polymer chains | 3 |
| Total formula weight | 45152.38 |
| Authors | Chatterjee, S.,Borek, D.,Otwinowski, Z.,Amarasinghe, G.K.,Leung, D.W. (deposition date: 2021-01-13, release date: 2021-03-17, Last modification date: 2024-04-03) |
| Primary citation | 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 Cited by 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: 33649232DOI: 10.1073/pnas.2020587118 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.82 Å) |
Structure validation
Download full validation report
