Cryo-EM structure of the respiratory syncytial virus RNA polymerase

The respiratory syncytial virus (RSV) RNA polymerase, constituted of a 250 kDa large (L) protein and tetrameric phosphoprotein (P), catalyzes three distinct enzymatic activities — nucleotide polymerization, cap addition, and cap methylation. How RSV L and P coordinate these activities is poorly understood. Here, we present a 3.67 Å cryo-EM structure of the RSV polymerase (L:P) complex. The structure reveals that the RNA dependent RNA polymerase (RdRp) and capping (Cap) domains of L interact with the oligomerization domain (P OD ) and C-terminal domain (P CTD ) of a tetramer of P. The density of the methyltransferase (MT) domain of L and the N-terminal domain of P (P NTD ) is missing. Further analysis and comparison with other RNA polymerases at different stages suggest the structure we obtained is likely to be at an elongation-compatible stage. Together, these data provide enriched insights into the interrelationship, the inhibitors, and the evolutionary implications of the RSV polymerase. Respiratory syncytial virus (RSV) is a pathogenic non-segmented negative-sense RNA virus and active RSV polymerase is composed of a 250 kDa large (L) protein and tetrameric phosphoprotein (P). Here, the authors present the 3.67 Å cryo-EM structure of the RSV polymerase (L:P) complex.