9VUI

Cryo-EM structure of the human measles virus RNA-dependent RNA polymerase complex bound to viral protein C

9VUI の概要

• エントリーDOI: 10.2210/pdb9vui/pdb
• EMDBエントリー: 65364
• 分子名称: Maltose/maltodextrin-binding periplasmic protein,Phosphoprotein, Maltose/maltodextrin-binding periplasmic protein,RNA-directed RNA polymerase L,Strep II and FLAG tag, Maltose/maltodextrin-binding periplasmic protein,Protein C,Green fluorescent protein, ... (5 entities in total)
• 機能のキーワード: measles virus rna-dependent rna polymerase complex bound to viral protein c, viral protein
• 由来する生物種: Escherichia coli K-12; 詳細
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 751378.28

構造登録者

Du, T.,Wang, J.,Wu, S.,Ru, H. (登録日: 2025-07-13, 公開日: 2026-05-27)

主引用文献

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

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: 41941628
DOI: 10.1073/pnas.2522978123

実験手法

ELECTRON MICROSCOPY (2.72 Å)