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Publication Abstract from PubMed

Nipah virus (NiV) and related viruses form a distinct henipavirus genus within the Paramyxoviridae family. NiV continues to spillover into the humans causing deadly outbreaks with increasing human-bat interaction. NiV encodes the large protein (L) and phosphoprotein (P) to form the viral RNA polymerase machinery. Their sequences show limited homologies to those of non-henipavirus paramyxoviruses. We report two cryo-electron microscopy (cryo-EM) structures of the Nipah virus (NiV) polymerase L-P complex, expressed and purified in either its full-length or truncated form. The structures resolve the RNA-dependent RNA polymerase (RdRp) and polyribonucleotidyl transferase (PRNTase) domains of the L protein, as well as a tetrameric P protein bundle bound to the L-RdRp. L-protein C-terminal regions are unresolved, indicating flexibility. Two PRNTase domain zinc-binding sites, conserved in most Mononegavirales, are confirmed essential for NiV polymerase activity. The structures further reveal anchoring of the P protein bundle and P protein X domain (XD) linkers on L, via an interaction pattern distinct among Paramyxoviridae. These interactions facilitate binding of a P protein XD linker in the nucleotide entry channel and distinct positioning of other XD linkers. We show that the disruption of the L-P interactions reduces NiV polymerase activity. The reported structures should facilitate rational antiviral-drug discovery and provide a guide for the functional study of NiV polymerase.

Cryo-EM structures of Nipah virus polymerase complex reveal highly varied interactions between L and P proteins among paramyxoviruses.,Xue L, Chang T, Gui J, Li Z, Zhao H, Zou B, Lu J, Li M, Wen X, Gao S, Zhan P, Rong L, Feng L, Gong P, He J, Chen X, Xiong X Protein Cell. 2025 Feb 18:pwaf014. doi: 10.1093/procel/pwaf014. PMID:39964914^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.