title: NS4A regulates the ATPase activity of the NS3 helicase: a novel cofactor role of the non-structural protein NS4A from West Nile virus.
abstract: Using constructs that encode the individual West Nile virus (WNV) NS3helicase (NS3hel) and NS3hel linked to the hydrophilic, N-terminal 1-50 sequence of NS4A, we demonstrated that the presence of NS4A allows NS3hel to conserve energy in the course of oligonucleotide substrate unwinding. Using NS4A mutants, we also determined that the C-terminal acidic EELPD/E motif of NS4A, which appears to be functionally similar to the acidic EFDEMEE motif of hepatitis C virus (HCV) NS4A, is essential for regulating the ATPase activity of NS3hel. We concluded that, similar to HCV NS4A, NS4A of WNV acts as a cofactor for NS3hel and allows helicase to sustain the unwinding rate of the viral RNA under conditions of ATP deficiency.
authors.affiliation: Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Shiryaev
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Chernov
authors.forename: Alexander E
authors.initials: AE
authors.lastname: Aleshin
authors.forename: Tatiana N
authors.initials: TN
authors.lastname: Shiryaeva
authors.forename: Alex Y
authors.initials: AY
authors.lastname: Strongin
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D003067:Coenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004265:DNA Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D015967:Gene Expression Regulation, Viral; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014902:West Nile virus / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics
chemical_list: D003067:Coenzymes; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; D000255:Adenosine Triphosphate; D004265:DNA Helicases