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The NS5A protein of bovine viral diarrhea virus contains an essential zinc-binding site similar to that of the hepatitis C virus NS5A protein

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Overview

authors

  • Tellinghuisen, Timothy
  • Paulson, M. S.
  • Rice, C. M.

publication date

  • August 2006

journal

  • Journal of Virology  Journal

abstract

  • The recent demonstration that the NS5A protein of hepatitis C virus (HCV) contains an unconventional zinc-binding site with the format Cx(17)CxCx(20)C and the presence of a similar sequence element in the NS5A proteins of members of the Pestivirus genus has led to the hypothesis that the NS5A protein of the pestivirus bovine viral diarrhea virus (BVDV) is a zinc-binding protein. A method for the expression and partial purification of BVDV NS5A was developed, and the partially purified protein was analyzed for zinc content by atomic absorption spectroscopy. BVDV NS5A was found to coordinate a single zinc atom per protein molecule. Mutation of any of the four cysteines of the predicted zinc-binding motif eliminated zinc coordination. Furthermore, analysis of mutations at these cysteine residues in the context of a BVDV replicon system indicated that these residues were absolutely essential for RNA replication. The recently determined crystal structure of the N-terminal zinc-binding domain of the HCV NS5A protein, combined with secondary structure predictions of the region surrounding the mapped BVDV zinc-binding region, indicates that the BVDV zinc-binding motif fits the general template Cx(22)CxCx(24)C and likely comprises a three-stranded antiparallel beta-sheet fold. These data highlight the similarities between the Hepacivirus and Pestivirus NS5A proteins and suggest that both proteins perform a not-yet-defined function in RNA replication that requires coordination of a single zinc atom.

subject areas

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cattle
  • Cloning, Molecular
  • Diarrhea Viruses, Bovine Viral
  • Hepacivirus
  • Molecular Sequence Data
  • Protein Binding
  • Protein Structure, Secondary
  • RNA Replicase
  • RNA, Viral
  • Sequence Homology, Amino Acid
  • Viral Nonstructural Proteins
  • Zinc
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Identity

PubMed Central ID

  • PMC1563740

International Standard Serial Number (ISSN)

  • 0022-538X

Digital Object Identifier (DOI)

  • 10.1128/jvi.00358-06

PubMed ID

  • 16840325
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Additional Document Info

start page

  • 7450

end page

  • 7458

volume

  • 80

issue

  • 15

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