The structure of the RNA-dependent RNA polymerase from bovine viral diarrhea virus establishes the role of GTP in de novo initiation

Kyung Choi, James M. Groarke, Dorothy C. Young, Richard J. Kuhn, Janet L. Smith, Daniel C. Pevear, Michael G. Rossmann

Research output: Contribution to journalArticle

167 Citations (Scopus)

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-Å 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.

Original languageEnglish (US)
Pages (from-to)4425-4430
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number13
DOIs
StatePublished - Mar 30 2004
Externally publishedYes

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Bovine Viral Diarrhea Viruses
RNA Replicase
Guanosine Triphosphate
Thumb
RNA
Fingers
Binding Sites

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

The structure of the RNA-dependent RNA polymerase from bovine viral diarrhea virus establishes the role of GTP in de novo initiation. / Choi, Kyung; Groarke, James M.; Young, Dorothy C.; Kuhn, Richard J.; Smith, Janet L.; Pevear, Daniel C.; Rossmann, Michael G.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 13, 30.03.2004, p. 4425-4430.

Research output: Contribution to journalArticle

Choi, Kyung ; Groarke, James M. ; Young, Dorothy C. ; Kuhn, Richard J. ; Smith, Janet L. ; Pevear, Daniel C. ; Rossmann, Michael G. / The structure of the RNA-dependent RNA polymerase from bovine viral diarrhea virus establishes the role of GTP in de novo initiation. In: Proceedings of the National Academy of Sciences of the United States of America. 2004 ; Vol. 101, No. 13. pp. 4425-4430.
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