title: Hepatitis C virus NS5A is able to competitively displace c-Myc from the Bin1 SH3 domain in vitro.
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.
authors.affiliation: Institut für Physikalische Biologie, Heinrich-Heine-Universität, 40225, Düsseldorf, Germany; Institute of Complex Systems (ICS-6) Structural Biochemistry, Forschungszentrum Jülich, 52425, Jülich, Germany.
authors.forename: Amine
authors.initials: A
authors.lastname: Aladag
authors.forename: Silke
authors.initials: S
authors.lastname: Hoffmann
authors.forename: Matthias
authors.initials: M
authors.lastname: Stoldt
authors.forename: Christina
authors.initials: C
authors.lastname: Bösing
authors.forename: Dieter
authors.initials: D
authors.lastname: Willbold
authors.forename: Melanie
authors.initials: M
authors.lastname: Schwarten
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000378:metabolism*; D017209:Apoptosis; D001667:Binding, Competitive; D002151:Calorimetry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000737:chemistry / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D025521:Tumor Suppressor Proteins / Q000737:chemistry* / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000378:metabolism*; D018909:src Homology Domains; D012324:RNA-Dependent RNA Polymerase
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D025521:Tumor Suppressor Proteins; D017361:Viral Nonstructural Proteins; C101410:BIN1 protein, human; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: Bin1; HCV; NMR; NS5A; SH3; protein-peptide interaction