Hepatitis C virus NS5A is able to competitively displace c-Myc from the Bin1 SH3 domain in vitro

J Pept Sci. 2014 May;20(5):334-40. doi: 10.1002/psc.2618. Epub 2014 Feb 24.

Abstract

We studied the interaction of the SH3 domain of Bin1 with a 15-mer peptide of HCV NS5A and show its potency to competitively displace a 15-mer human c-Myc fragment, which is a physiological ligand of Bin1, using NMR spectroscopy. Fluorescence spectroscopy and ITC were employed to determine the affinity of Bin1 SH3 to NS5A(347-361), yielding a submicromolar affinity to NS5A. Our study compares the binding dynamics and affinities of the relevant regions for binding of c-Myc and NS5A to Bin1 SH3. The result gives further insights into the potential role of NS5A in Bin1-mediated apoptosis.

Keywords: Bin1; HCV; NMR; NS5A; SH3; protein-peptide interaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry*
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Apoptosis
  • Binding, Competitive
  • Calorimetry
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / metabolism*
  • Proto-Oncogene Proteins c-myc / chemistry
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Spectrometry, Fluorescence
  • Tumor Suppressor Proteins / chemistry*
  • Tumor Suppressor Proteins / metabolism*
  • Viral Nonstructural Proteins / chemistry
  • Viral Nonstructural Proteins / metabolism*
  • src Homology Domains*

Substances

  • Adaptor Proteins, Signal Transducing
  • BIN1 protein, human
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-myc
  • Tumor Suppressor Proteins
  • Viral Nonstructural Proteins
  • NS-5 protein, hepatitis C virus