Structure of the Flavivirus helicase: implications for catalytic activity, protein interactions, and proteolytic processing.
Yellow fever virus (YFV), a member of the Flavivirus genus, has a plus-sense RNA genome encoding a single polyprotein. Viral protein NS3 includes a protease and a helicase that are essential to virus replication and to RNA capping. The 1.8-A crystal structure of the helicase region of the YFV NS3 protein includes residues 187 to 623. Two familiar helicase domains bind nucleotide in a triphosphate pocket without base recognition, providing a site for nonspecific hydrolysis of nucleoside triphosphates and RNA triphosphate. The third, C-terminal domain has a unique structure and is proposed to function in RNA and protein recognition. The organization of the three domains indicates that cleavage of the viral polyprotein NS3-NS4A junction occurs in trans.
Wu
Jinhua
J
Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907, USA.
Bera
Aloke Kumar
AK
Kuhn
Richard J
RJ
Smith
Janet L
JL
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D002384:Catalysis; D005416:Flavivirus / Q000201:enzymology*; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D020365:RNA Helicases / Q000737:chemistry / Q000502:physiology; D012697:Serine Endopeptidases / Q000737:chemistry / Q000502:physiology; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000502:physiology; D014902:West Nile virus / Q000201:enzymology*; D015005:Yellow fever virus / Q000201:enzymology*; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000251:Adenosine Triphosphatases; D012313:RNA; D020365:RNA Helicases; D012697:Serine Endopeptidases; D017361:Viral Nonstructural Proteins; C060028:NS3 protein, flavivirus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases