Structure of the hepatitis C virus RNA helicase domain

Nat Struct Biol. 1997 Jun;4(6):463-7. doi: 10.1038/nsb0697-463.

Abstract

Helicases are nucleotide triphosphate (NTP)-dependent enzymes responsible for unwinding duplex DNA and RNA during genomic replication. The 2.1 A resolution structure of the HCV helicase from the positive-stranded RNA hepatitis C virus reveals a molecule with distinct NTPase and RNA binding domains. The structure supports a mechanism of helicase activity involving initial recognition of the requisite 3' single-stranded region on the nucleic acid substrate by a conserved arginine-rich sequence on the RNA binding domain. Comparison of crystallographically independent molecules shows that rotation of the RNA binding domain involves conformational changes within a conserved TATPP sequence and untwisting of an extended antiparallel beta-sheet. Location of the TATPP sequence at the end of an NTPase domain beta-strand structurally homologous to the 'switch region' of many NTP-dependent enzymes offers the possibility that domain rotation is coupled to NTP hydrolysis in the helicase catalytic cycle.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Computer Simulation
  • Conserved Sequence
  • Crystallography, X-Ray
  • DNA Helicases / chemistry
  • DNA Helicases / metabolism
  • Hydrolysis
  • Models, Molecular
  • Protein Conformation
  • RNA Helicases
  • RNA Nucleotidyltransferases / chemistry
  • RNA Nucleotidyltransferases / metabolism*
  • RNA, Viral / metabolism
  • Substrate Specificity
  • Viral Nonstructural Proteins / chemistry*
  • Viral Nonstructural Proteins / metabolism*

Substances

  • NS3 protein, hepatitis C virus
  • RNA, Viral
  • Viral Nonstructural Proteins
  • RNA Nucleotidyltransferases
  • DNA Helicases
  • RNA Helicases