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

Authors

  • Amine Aladag,

    1. Institut für Physikalische Biologie, Heinrich-Heine-Universität, Düsseldorf, Germany
    2. Institute of Complex Systems (ICS-6) Structural Biochemistry, Forschungszentrum Jülich, Jülich, Germany
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  • Silke Hoffmann,

    1. Institute of Complex Systems (ICS-6) Structural Biochemistry, Forschungszentrum Jülich, Jülich, Germany
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  • Matthias Stoldt,

    1. Institut für Physikalische Biologie, Heinrich-Heine-Universität, Düsseldorf, Germany
    2. Institute of Complex Systems (ICS-6) Structural Biochemistry, Forschungszentrum Jülich, Jülich, Germany
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  • Christina Bösing,

    1. Institut für Physikalische Biologie, Heinrich-Heine-Universität, Düsseldorf, Germany
    2. Institute of Complex Systems (ICS-6) Structural Biochemistry, Forschungszentrum Jülich, Jülich, Germany
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  • Dieter Willbold,

    1. Institut für Physikalische Biologie, Heinrich-Heine-Universität, Düsseldorf, Germany
    2. Institute of Complex Systems (ICS-6) Structural Biochemistry, Forschungszentrum Jülich, Jülich, Germany
    3. Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Grenoble, France
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  • Melanie Schwarten

    Corresponding author
    1. Institute of Complex Systems (ICS-6) Structural Biochemistry, Forschungszentrum Jülich, Jülich, Germany
    2. Institut de Biologie Structurale, Université Grenoble 1, Grenoble Cedex 1, France
    3. Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Grenoble, France
    4. Centre National de Recherche Scientifique (CNRS), Grenoble, France
    • Correspondence to: Melanie Schwarten, Institute of Complex Systems (ICS-6) Structural Biochemistry, Forschungszentrum Jülich, 52425 Jülich, Germany. E-mail: m.schwarten@fz-juelich.de

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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. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.

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