9IV9

Cryo-EM structure of a truncated Nipah Virus L Protein bound by Phosphoprotein Tetramer

Summary for 9IV9

• Entry DOI: 10.2210/pdb9iv9/pdb
• EMDB information: 60922
• Descriptor: RNA-directed RNA polymerase L, Phosphoprotein, ZINC ION (3 entities in total)
• Functional Keywords: rna polymerase, viral protein
• Biological source: Henipavirus nipahense; More
• Total number of polymer chains: 5
• Total formula weight: 479958.99

Authors

Xue, L.,Chang, T.,Gui, J.,Li, Z.,Zhao, H.,Zou, B.,Li, M.,He, J.,Chen, X.,Xiong, X. (deposition date: 2024-07-23, release date: 2025-05-21)

Primary citation

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.
Cryo-EM structures of Nipah virus polymerase complex reveal highly varied interactions between L and P proteins among paramyxoviruses.
Protein Cell, 2025

PubMed Abstract: 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.

PubMed: 39964914
DOI: 10.1093/procel/pwaf014

Experimental method

ELECTRON MICROSCOPY (2.31 Å)