9BDQ

The structure of NiV L-P complex

9BDQ の概要

• エントリーDOI: 10.2210/pdb9bdq/pdb
• EMDBエントリー: 44465
• 分子名称: RNA-directed RNA polymerase L, Phosphoprotein, ZINC ION (3 entities in total)
• 機能のキーワード: rdrp complex, l-p complex, nipah virus, viral protein
• 由来する生物種: Henipavirus nipahense; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 570288.44

構造登録者

Hu, S.,Yang, P.,Yu, Z.,Abraham, J. (登録日: 2024-04-12, 公開日: 2025-01-29, 最終更新日: 2025-06-04)

主引用文献

Hu, S.,Kim, H.,Yang, P.,Yu, Z.,Ludeke, B.,Mobilia, S.,Pan, J.,Stratton, M.,Bian, Y.,Fearns, R.,Abraham, J.
Structural and functional analysis of the Nipah virus polymerase complex.
Cell, 188:688-703.e18, 2025

PubMed Abstract: Nipah virus (NiV) is a bat-borne, zoonotic RNA virus that is highly pathogenic in humans. The NiV polymerase, which mediates viral genome replication and mRNA transcription, is a promising drug target. We determined the cryoelectron microscopy (cryo-EM) structure of the NiV polymerase complex, comprising the large protein (L) and phosphoprotein (P), and performed structural, biophysical, and in-depth functional analyses of the NiV polymerase. The L protein assembles with a long P tetrameric coiled-coil that is capped by a bundle of ⍺-helices that we show are likely dynamic in solution. Docking studies with a known L inhibitor clarify mechanisms of antiviral drug resistance. In addition, we identified L protein features that are required for both transcription and RNA replication and mutations that have a greater impact on RNA replication than on transcription. Our findings have the potential to aid in the rational development of drugs to combat NiV infection.

PubMed: 39837328
DOI: 10.1016/j.cell.2024.12.021

実験手法

ELECTRON MICROSCOPY (2.26 Å)