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 language | English (US) |
|---|---|
| Pages (from-to) | 4425-4430 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 101 |
| Issue number | 13 |
| DOIs | |
| State | Published - Mar 30 2004 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Genetics
- General
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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 journal › Article
}
TY - JOUR
T1 - The structure of the RNA-dependent RNA polymerase from bovine viral diarrhea virus establishes the role of GTP in de novo initiation
AU - Choi, Kyung
AU - Groarke, James M.
AU - Young, Dorothy C.
AU - Kuhn, Richard J.
AU - Smith, Janet L.
AU - Pevear, Daniel C.
AU - Rossmann, Michael G.
PY - 2004/3/30
Y1 - 2004/3/30
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=1842481188&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=1842481188&partnerID=8YFLogxK
U2 - 10.1073/pnas.0400660101
DO - 10.1073/pnas.0400660101
M3 - Article
C2 - 15070734
AN - SCOPUS:1842481188
VL - 101
SP - 4425
EP - 4430
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 13
ER -