9VUM
Cryo-EM structure of the Nipah virus RNA-dependent RNA polymerase complex bound to allosteric inhibitor ERDRP-0519
This is a non-PDB format compatible entry.
Summary for 9VUM
| Entry DOI | 10.2210/pdb9vum/pdb |
| Related | 9VUI |
| EMDB information | 65368 |
| Descriptor | Maltose/maltodextrin-binding periplasmic protein,RNA-directed RNA polymerase L, Maltose/maltodextrin-binding periplasmic protein,Phosphoprotein, ZINC ION, ... (5 entities in total) |
| Functional Keywords | rna-dependent rna polymerase complex bound to allosteric inhibitor erdrp-0519, viral protein |
| Biological source | Escherichia coli K-12 More |
| Total number of polymer chains | 5 |
| Total formula weight | 500471.47 |
| Authors | |
| Primary citation | Du, T.,Wang, J.,Yang, C.,Xue, R.,Chen, Y.,Jie, K.,Zhang, X.,Zhang, L.,Song, G.,Zhang, Q.,Wu, S.,Ru, H. Structural insights into measles virus RNA synthesis regulation and pan-paramyxoviral polymerase inhibition by ERDRP-0519. Proc.Natl.Acad.Sci.USA, 123:e2522978123-e2522978123, 2026 Cited by PubMed Abstract: Nonsegmented negative-sense RNA viruses (nsNSVs) rely on a multifunctional RNA-dependent RNA polymerase (RdRP) complex for transcription and replication. In measles virus (MeV), the nonstructural protein C has long been implicated in regulating RNA synthesis, yet its precise role remains unclear. Here, we show that the MeV C protein directly associates with the RdRP complex. Using cryoelectron microscopy, we determined atomic-resolution structures of the MeV polymerase with and without C, revealing that C binding stabilizes the C-terminal region of L and locks the complex into a replication-competent elongation state. Biochemical data further show that C promotes N protein recruitment, enhancing polymerase processivity through facilitating encapsidation during replication. Additionally, we also resolved high-resolution structures of MeV and Nipah virus (NiV) polymerases bound to ERDRP-0519, an orally available morbillivirus inhibitor. Unexpectedly, the compound occupies an allosteric pocket within the RdRp domain rather than the previously predicted PRNTase domain, overlapping conserved resistance sites. This binding induces conformational changes in palm subdomain, blocking RNA template and nucleotide engagement, thereby halting RNA synthesis. These findings uncover distinct regulatory and inhibitory mechanisms in paramyxovirus polymerases and provide a structural framework for the rational design of broad-spectrum antivirals targeting MeV, NiV, and potentially other clinically relevant nsNSVs. PubMed: 41941628DOI: 10.1073/pnas.2522978123 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.84 Å) |
Structure validation
Download full validation report
