Cryo-EM structure of the respiratory syncytial virus RNA polymerase

Nat Commun. 2020 Jan 17;11(1):368. doi: 10.1038/s41467-019-14246-3.

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 (POD) and C-terminal domain (PCTD) of a tetramer of P. The density of the methyltransferase (MT) domain of L and the N-terminal domain of P (PNTD) 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cryoelectron Microscopy*
  • DNA-Directed RNA Polymerases / chemistry*
  • DNA-Directed RNA Polymerases / genetics
  • DNA-Directed RNA Polymerases / metabolism
  • Models, Molecular
  • Phosphoproteins / chemistry
  • Protein Conformation
  • Protein Domains
  • RNA-Dependent RNA Polymerase / chemistry*
  • RNA-Dependent RNA Polymerase / genetics
  • RNA-Dependent RNA Polymerase / metabolism
  • Respiratory Syncytial Virus Infections / virology
  • Respiratory Syncytial Virus, Human / enzymology*
  • Respiratory Syncytial Virus, Human / genetics
  • Viral Proteins / chemistry*
  • Viral Structures

Substances

  • Phosphoproteins
  • Viral Proteins
  • RNA-Dependent RNA Polymerase
  • DNA-Directed RNA Polymerases