9MZH

Cryo-EM structure of the Nipah virus polymerase containing the connecting domain

9MZH の概要

• エントリーDOI: 10.2210/pdb9mzh/pdb
• 関連するPDBエントリー: 9COK 9MUW
• EMDBエントリー: 45896
• 分子名称: Phosphoprotein, RNA-directed RNA polymerase L (2 entities in total)
• 機能のキーワード: nipah virus, polymerase, connecting domain, viral protein, transferase
• 由来する生物種: Henipavirus nipahense; 詳細
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 941409.33

構造登録者

Chen, Z.H.,Liang, B. (登録日: 2025-01-23, 公開日: 2025-07-30, 最終更新日: 2025-11-05)

主引用文献

Chen, Z.,Quirit Dudley, J.,Deniston, C.,Buffalo, C.Z.,Patra, D.,Cao, D.,Hunt, J.,Rohaim, A.,Sengupta, D.,Wen, L.,Tsang, T.,Xie, L.,DiDonato, M.,Spraggon, G.,Clifton, M.C.,Jarrousse, N.,Straimer, J.,Liang, B.
Cryo-EM structures of Nipah virus polymerases and high-throughput RdRp assay development enable anti-NiV drug discovery.
Nat Commun, 16:6655-6655, 2025

PubMed Abstract: Transcription and replication of the Nipah virus (NiV) are driven by the large protein (L) together with its essential co-factor phosphoprotein (P). L encodes all the viral enzymatic functions, including RNA-dependent RNA polymerase (RdRp) activity, while the tetrameric P is multi-modular. Here, we investigate the molecular mechanism of the NiV polymerase and build tools for anti-NiV drug discovery. We analyze and compare multiple cryo-EM structures of both full-length and truncated NiV polymerases from the Malaysia and Bangladesh strains. We identify two conserved loops in the polyribonucleotidyltransferase (PRNTase) domain of L and the binding between RdRp-PRNTase and CD domains. To further assess the mechanism of NiV polymerase activity, we establish a highly sensitive radioactive-labeled RNA synthesis assay and identify a back-priming activity in the NiV polymerase as well as a fluorescence and luminescent-based non-radioactive polymerase assay to enable high-throughput screening for L protein inhibitors. The combination of structural analysis and the development of both high-sensitive and high-throughput biochemical assays will enable the identification of new direct-acting antiviral candidates for treating highly pathogenic henipaviruses.

PubMed: 40683863
DOI: 10.1038/s41467-025-61764-4

実験手法

ELECTRON MICROSCOPY (2.99 Å)