1s49

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Crystal Structure of RNA-dependent RNA polymerase construct 1 (residues 71-679) from bovine viral diarrhea virus complexed with GTP

Structural highlights

1s49 is a 1 chain structure with sequence from Bovine viral diarrhea virus 1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3Å
Ligands:GTP, MSE
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

POLG_BVDVN Initial binding to target cell probably involves interaction of E(rns) with glycosaminoglycans. E1 and/or E2 are responsible of cell attachment with CD46 and subsequent fusion after internalization of the virion by endocytosis (Probable).[1] [2] P7 forms a leader sequence to properly orient NS2 in the membrane (By similarity).[3] [4] Uncleaved NS2-3 is required for production of infectious virus.[5] [6] NS2 protease seems to play a vital role in viral RNA replication control and in the pathogenicity of the virus.[7] [8] NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase.[9] [10] NS4A is a cofactor for the NS3 protease activity (By similarity).[11] [12] RNA-directed RNA polymerase NS5 replicates the viral (+) and (-) genome.[13] [14]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

The structure of the RNA-dependent RNA polymerase from bovine viral diarrhea virus establishes the role of GTP in de novo initiation.,Choi KH, Groarke JM, Young DC, Kuhn RJ, Smith JL, Pevear DC, Rossmann MG Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4425-30. Epub 2004 Mar 19. PMID:15070734[15]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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See Also

References

  1. ↑ Agapov EV, Murray CL, Frolov I, Qu L, Myers TM, Rice CM. Uncleaved NS2-3 is required for production of infectious bovine viral diarrhea virus. J Virol. 2004 Mar;78(5):2414-25. PMID:14963137
  2. ↑ Lecot S, Belouzard S, Dubuisson J, Rouille Y. Bovine viral diarrhea virus entry is dependent on clathrin-mediated endocytosis. J Virol. 2005 Aug;79(16):10826-9. PMID:16051874 doi:10.1128/JVI.79.16.10826-10829.2005
  3. ↑ Agapov EV, Murray CL, Frolov I, Qu L, Myers TM, Rice CM. Uncleaved NS2-3 is required for production of infectious bovine viral diarrhea virus. J Virol. 2004 Mar;78(5):2414-25. PMID:14963137
  4. ↑ Lecot S, Belouzard S, Dubuisson J, Rouille Y. Bovine viral diarrhea virus entry is dependent on clathrin-mediated endocytosis. J Virol. 2005 Aug;79(16):10826-9. PMID:16051874 doi:10.1128/JVI.79.16.10826-10829.2005
  5. ↑ Agapov EV, Murray CL, Frolov I, Qu L, Myers TM, Rice CM. Uncleaved NS2-3 is required for production of infectious bovine viral diarrhea virus. J Virol. 2004 Mar;78(5):2414-25. PMID:14963137
  6. ↑ Lecot S, Belouzard S, Dubuisson J, Rouille Y. Bovine viral diarrhea virus entry is dependent on clathrin-mediated endocytosis. J Virol. 2005 Aug;79(16):10826-9. PMID:16051874 doi:10.1128/JVI.79.16.10826-10829.2005
  7. ↑ Agapov EV, Murray CL, Frolov I, Qu L, Myers TM, Rice CM. Uncleaved NS2-3 is required for production of infectious bovine viral diarrhea virus. J Virol. 2004 Mar;78(5):2414-25. PMID:14963137
  8. ↑ Lecot S, Belouzard S, Dubuisson J, Rouille Y. Bovine viral diarrhea virus entry is dependent on clathrin-mediated endocytosis. J Virol. 2005 Aug;79(16):10826-9. PMID:16051874 doi:10.1128/JVI.79.16.10826-10829.2005
  9. ↑ Agapov EV, Murray CL, Frolov I, Qu L, Myers TM, Rice CM. Uncleaved NS2-3 is required for production of infectious bovine viral diarrhea virus. J Virol. 2004 Mar;78(5):2414-25. PMID:14963137
  10. ↑ Lecot S, Belouzard S, Dubuisson J, Rouille Y. Bovine viral diarrhea virus entry is dependent on clathrin-mediated endocytosis. J Virol. 2005 Aug;79(16):10826-9. PMID:16051874 doi:10.1128/JVI.79.16.10826-10829.2005
  11. ↑ Agapov EV, Murray CL, Frolov I, Qu L, Myers TM, Rice CM. Uncleaved NS2-3 is required for production of infectious bovine viral diarrhea virus. J Virol. 2004 Mar;78(5):2414-25. PMID:14963137
  12. ↑ Lecot S, Belouzard S, Dubuisson J, Rouille Y. Bovine viral diarrhea virus entry is dependent on clathrin-mediated endocytosis. J Virol. 2005 Aug;79(16):10826-9. PMID:16051874 doi:10.1128/JVI.79.16.10826-10829.2005
  13. ↑ Agapov EV, Murray CL, Frolov I, Qu L, Myers TM, Rice CM. Uncleaved NS2-3 is required for production of infectious bovine viral diarrhea virus. J Virol. 2004 Mar;78(5):2414-25. PMID:14963137
  14. ↑ Lecot S, Belouzard S, Dubuisson J, Rouille Y. Bovine viral diarrhea virus entry is dependent on clathrin-mediated endocytosis. J Virol. 2005 Aug;79(16):10826-9. PMID:16051874 doi:10.1128/JVI.79.16.10826-10829.2005
  15. ↑ Choi KH, Groarke JM, Young DC, Kuhn RJ, Smith JL, Pevear DC, Rossmann MG. The structure of the RNA-dependent RNA polymerase from bovine viral diarrhea virus establishes the role of GTP in de novo initiation. Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4425-30. Epub 2004 Mar 19. PMID:15070734 doi:10.1073/pnas.0400660101

Contents


PDB ID 1s49

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