Structure of the RNA-dependent RNA polymerase of poliovirus

Structure. 1997 Aug 15;5(8):1109-22. doi: 10.1016/s0969-2126(97)00261-x.

Abstract

Background: The central player in the replication of RNA viruses is the viral RNA-dependent RNA polymerase. The 53 kDa poliovirus polymerase, together with other viral and possibly host proteins, carries out viral RNA replication in the host cell cytoplasm. RNA-dependent RNA polymerases comprise a distinct category of polymerases that have limited sequence similarity to reverse transcriptases (RNA-dependent DNA polymerases) and perhaps also to DNA-dependent polymerases. Previously reported structures of RNA-dependent DNA polymerases, DNA-dependent DNA polymerases and a DNA-dependent RNA polymerase show that structural and evolutionary relationships exist between the different polymerase categories.

Results: We have determined the structure of the RNA-dependent RNA polymerase of poliovirus at 2.6 A resolution by X-ray crystallography. It has the same overall shape as other polymerases, commonly described by analogy to a right hand. The structures of the 'fingers' and 'thumb' subdomains of poliovirus polymerase differ from those of other polymerases, but the palm subdomain contains a core structure very similar to that of other polymerases. This conserved core structure is composed of four of the amino acid sequence motifs described for RNA-dependent polymerases. Structure-based alignments of these motifs has enabled us to modify and extend previous sequence and structural alignments so as to relate sequence conservation to function. Extensive regions of polymerase-polymerase interactions observed in the crystals suggest an unusual higher order structure that we believe is important for polymerase function.

Conclusions: As a first example of a structure of an RNA-dependent RNA polymerase, the poliovirus polymerase structure provides for a better understanding of polymerase structure, function and evolution. In addition, it has yielded insights into an unusual higher order structure that may be critical for poliovirus polymerase function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Conserved Sequence
  • Crystallography, X-Ray
  • Molecular Sequence Data
  • Poliovirus / enzymology*
  • Protein Conformation*
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • RNA Replicase / chemistry*

Substances

  • RNA Replicase