Cryo-EM structure of the respiratory syncytial virus RNA polymerase.

Cao, Dongdong; Gao, Yunrong; Roesler, Claire; Rice, Samantha; D'Cunha, Paul; Zhuang, Lisa; Slack, Julia; Domke, Mason et al. · Nat Commun · 2020

basic_science · Level V

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Abstract

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<sub>OD</sub>) and C-terminal domain (P<sub>CTD</sub>) of a tetramer of P. The density of the methyltransferase (MT) domain of L and the N-terminal domain of P (P<sub>NTD</sub>) 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.

Medical subject headings