6PZK
Cryo-EM Structure of the Respiratory Syncytial Virus Polymerase (L) Protein Bound by the Tetrameric Phosphoprotein (P)
Summary for 6PZK
| Entry DOI | 10.2210/pdb6pzk/pdb |
| EMDB information | 20536 |
| Descriptor | RNA-directed RNA polymerase L, Phosphoprotein (2 entities in total) |
| Functional Keywords | rna-binding protein, rsv, rdrp, rna-dependent rna polymerase, prntase, polyribonucleotidyl transferase, rna capping, viral replication, viral protein |
| Biological source | Human respiratory syncytial virus A2 More |
| Total number of polymer chains | 5 |
| Total formula weight | 370734.33 |
| Authors | Gilman, M.S.A.,McLellan, J.S. (deposition date: 2019-08-01, release date: 2019-09-11, Last modification date: 2024-03-20) |
| Primary citation | Gilman, M.S.A.,Liu, C.,Fung, A.,Behera, I.,Jordan, P.,Rigaux, P.,Ysebaert, N.,Tcherniuk, S.,Sourimant, J.,Eleouet, J.F.,Sutto-Ortiz, P.,Decroly, E.,Roymans, D.,Jin, Z.,McLellan, J.S. Structure of the Respiratory Syncytial Virus Polymerase Complex. Cell, 179:193-204.e14, 2019 Cited by PubMed Abstract: Numerous interventions are in clinical development for respiratory syncytial virus (RSV) infection, including small molecules that target viral transcription and replication. These processes are catalyzed by a complex comprising the RNA-dependent RNA polymerase (L) and the tetrameric phosphoprotein (P). RSV P recruits multiple proteins to the polymerase complex and, with the exception of its oligomerization domain, is thought to be intrinsically disordered. Despite their critical roles in RSV transcription and replication, structures of L and P have remained elusive. Here, we describe the 3.2-Å cryo-EM structure of RSV L bound to tetrameric P. The structure reveals a striking tentacular arrangement of P, with each of the four monomers adopting a distinct conformation. The structure also rationalizes inhibitor escape mutants and mutations observed in live-attenuated vaccine candidates. These results provide a framework for determining the molecular underpinnings of RSV replication and transcription and should facilitate the design of effective RSV inhibitors. PubMed: 31495574DOI: 10.1016/j.cell.2019.08.014 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.2 Å) |
Structure validation
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