Domain 3 of non-structural protein 5A from hepatitis C virus is natively unfolded

Biochem Biophys Res Commun. 2009 Apr 17;381(4):634-8. doi: 10.1016/j.bbrc.2009.02.108. Epub 2009 Feb 26.

Abstract

Hepatitis C virus (HCV) non-structural protein 5A (NS5A) is involved both in the viral replication and particle production. Its third domain (NS5A-D3), although not absolutely required for replication, is a key determinant for the production and assembly of novel HCV particles. As a prerequisite to elucidate the precise functions of this domain, we report here the first molecular characterization of purified recombinant HCV NS5A-D3. Sequence analysis indicates that NS5A-D3 is mostly unstructured but that short structural elements may exist at its N-terminus. Gel filtration chromatography, circular dichroism and finally NMR spectroscopy all point out the natively unfolded nature of purified recombinant NS5A-D3. This lack of stable folding is thought to be essential for primary interactions of NS5A-D3 domain with other viral or host proteins, which could stabilize some specific conformations conferring new functional features.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Hepacivirus / metabolism*
  • Molecular Sequence Data
  • Protein Folding
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Viral Nonstructural Proteins / chemistry*
  • Viral Nonstructural Proteins / genetics

Substances

  • NS-5 protein, hepatitis C virus
  • Recombinant Proteins
  • Viral Nonstructural Proteins