9IR3

Cryo-EM structure of Nipah virus L-P polymerase complex

Summary for 9IR3

• Entry DOI: 10.2210/pdb9ir3/pdb
• EMDB information: 60799
• Descriptor: RNA-directed RNA polymerase L, Phosphoprotein, ZINC ION (3 entities in total)
• Functional Keywords: niv, polymerase, replication, cryo-em, transcription
• Biological source: Nipah virus; More
• Total number of polymer chains: 6
• Total formula weight: 649647.57

Authors

Shi, Y.,Peng, Q. (deposition date: 2024-07-13, release date: 2024-12-11, Last modification date: 2024-12-25)

Primary citation

Peng, Q.,Dong, Y.,Jia, M.,Liu, Q.,Bi, Y.,Qi, J.,Shi, Y.
Cryo-EM structure of Nipah virus L-P polymerase complex.
Nat Commun, 15:10524-10524, 2024

PubMed Abstract: Nipah virus (NiV) is a non-segmented, negative-strand (NNS) RNA virus, belonging to Paramyxoviridae. The RNA polymerase complex, composed of large (L) protein and tetrameric phosphoprotein (P), is responsible for genome transcription and replication by catalyzing NTP polymerization, mRNA capping and cap methylation. Here, we determine the cryo-electron microscopy (cryo-EM) structure of fully bioactive NiV L-P polymerase complex at a resolution of 3.19 Å. The L-P complex displays a conserved architecture like other NNS RNA virus polymerases and L interacts with the oligomerization domain and the extreme C-terminus region of P tetramer. Moreover, we elucidate that NiV is naturally resistant to the allosteric L-targeting inhibitor GHP-88309 due to the conformational change in the drug binding site. We also find that the non-nucleotide drug suramin can inhibit the NiV L-P polymerase activity at both the enzymatic and cellular levels. Our findings have greatly enhanced the molecular understanding of NiV genome replication and transcription and provided the rationale for broad-spectrum polymerase-targeted drug design.

PubMed: 39627254
DOI: 10.1038/s41467-024-54994-5

Experimental method

ELECTRON MICROSCOPY (3.19 Å)