Structure of the measles virus ternary polymerase complex

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_core-P and L_full-P-C. The L_core-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_full-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.