title: The structure of the RNA-dependent RNA polymerase from bovine viral diarrhea virus establishes the role of GTP in de novo initiation.
abstract: The bovine viral diarrhea virus (BVDV) RNA-dependent RNA polymerase can initiate RNA replication by a de novo mechanism without a primer. The structure of BVDV polymerase, determined to 2.9-A resolution, contains a unique N-terminal domain, in addition to the fingers, palm, and thumb domains common to other polymerases. The structure of BVDV polymerase complexed with GTP, which is required for de novo (primer-independent) initiation, shows that GTP binds adjacent to the initiation NTP, suggesting that the GTP mimics a vestigial RNA product. Comparison of five monomers in two different crystal forms showed conformational changes in the fingertip region and in the thumb domain that may help to translocate the RNA template and product strands during elongation. The putative binding sites of previously reported BVDV inhibitors are also discussed.
authors.affiliation: Department of Biological Sciences, Purdue University, 915 West State Street, West Lafayette, IN 47907, USA.
authors.forename: Kyung H
authors.initials: KH
authors.lastname: Choi
authors.forename: James M
authors.initials: JM
authors.lastname: Groarke
authors.forename: Dorothy C
authors.initials: DC
authors.lastname: Young
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Kuhn
authors.forename: Janet L
authors.initials: JL
authors.lastname: Smith
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Pevear
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rossmann
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D018360:Crystallography, X-Ray; D001908:Diarrhea Viruses, Bovine Viral / Q000201:enzymology*; D006160:Guanosine Triphosphate / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012324:RNA-Dependent RNA Polymerase / Q000737:chemistry* / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D006160:Guanosine Triphosphate; D012324:RNA-Dependent RNA Polymerase