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

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...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2004-03, Vol.101 (13), p.4425-4430
Main Authors: Choi, K.H, Groarke, J.M, Young, D.C, Kuhn, R.J, Smith, J.L, Pevear, D.C, Rossmann, M.G
Format: Article
Language:English
Subjects:
Active sites
Amino Acid Sequence
Animals
Biological Sciences
Biophysics
Bovine viral diarrhea virus
Cattle
Crystallography, X-Ray
Crystals
Diarrhea
Diarrhea Viruses, Bovine Viral - enzymology
Dimers
Enzymes
Fingers
Guanosine Triphosphate - chemistry
Guanosine Triphosphate - metabolism
Models, Molecular
Molecular Sequence Data
Molecules
Monomers
Protein Conformation
Protein Structure, Secondary
Proteins
Ribonucleic acid
RNA
RNA Replicase - chemistry
RNA Replicase - metabolism
Sequence Alignment
Sequence Homology, Amino Acid
Thumb
Viruses
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Summary: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 vestigal 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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0400660101