title: Structure of the hepatitis C virus RNA helicase domain.
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.
authors.affiliation: Structural Chemistry and Virology Department, Schering-Plough Research Institute, Kensworth, New Jersey 07033, USA.
authors.forename: N
authors.initials: N
authors.lastname: Yao
authors.forename: T
authors.initials: T
authors.lastname: Hesson
authors.forename: M
authors.initials: M
authors.lastname: Cable
authors.forename: Z
authors.initials: Z
authors.lastname: Hong
authors.forename: A D
authors.initials: AD
authors.lastname: Kwong
authors.forename: H V
authors.initials: HV
authors.lastname: Le
authors.forename: P C
authors.initials: PC
authors.lastname: Weber
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003198:Computer Simulation; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D004265:DNA Helicases / Q000737:chemistry / Q000378:metabolism; D006868:Hydrolysis; D008958:Models, Molecular; D011487:Protein Conformation; D020365:RNA Helicases; D012316:RNA Nucleotidyltransferases / Q000737:chemistry / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism; D013379:Substrate Specificity; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000378:metabolism*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D004265:DNA Helicases; D020365:RNA Helicases; D012316:RNA Nucleotidyltransferases; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases