9DUS

Cryo-EM structure of the Measles Virus polymerase (L) protein in complex with the tetrameric phosphoprotein (P)

Summary for 9DUS

• Entry DOI: 10.2210/pdb9dus/pdb
• EMDB information: 47176
• Descriptor: RNA-directed RNA polymerase L, Phosphoprotein (2 entities in total)
• Functional Keywords: measles virus, l protein, phosphoprotein, rna-dependent rna polymerase, prntase, gdp polyribonucleotidyl transferase, rna capping, mtase, viral replication, transferase, viral protein
• Biological source: Measles virus strain Edmonston-B; More
• Total number of polymer chains: 5
• Total formula weight: 464263.97

Authors

Liu, B.,Wang, D.,Yang, G. (deposition date: 2024-10-04, release date: 2025-04-09, Last modification date: 2025-04-30)

Primary citation

Wang, D.,Yang, G.,Liu, B.
Structure of the measles virus ternary polymerase complex.
Nat Commun, 16:3819-3819, 2025

PubMed Abstract: Measles virus (MeV) is a highly contagious pathogen that causes significant morbidity worldwide. Its polymerase machinery, composed of the large protein (L) and phosphoprotein (P), is crucial for viral replication and transcription, making it a promising target for antiviral drug development. Here we present cryo-electron microscopy structures of two distinct MeV polymerase complexes: L-P and L-P-C. The L-P complex characterizes the N-terminal domain, RNA-dependent RNA polymerase (RdRp), and GDP poly-ribonucleotidyltransferase of the L protein, along with the tetrameric P of varying lengths. The L-P-C complex reveals that C protein dimer binds at the cleft between RdRp and the flexible domains of the L protein: the connecting domain, methyltransferase domain, and C-terminal domain. This interaction results in the visualization of these domains and creates an extended RNA channel, remodeling the putative nascent replicated RNA exit and potentially regulating RNA synthesis processivity. Our findings reveal the architecture and molecular details of MeV polymerase complexes, providing new insights into their mechanisms and suggesting potential intervention targets for antiviral therapy.

PubMed: 40268911
DOI: 10.1038/s41467-025-58985-y

Experimental method

ELECTRON MICROSCOPY (3.12 Å)