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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred


SCImago Journal Rank (SJR) 2015: 1.607
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Impact per Publication (IPP) 2015: 2.609

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1437-4315
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Competitive displacement of full-length HIV-1 Nef from the Hck SH3 domain by a high-affinity artificial peptide

Thomas Stangler1 / Tuyen Tran2 / Silke Hoffmann3 / Holger Schmidt4 / Esther Jonas5 / Dieter Willbold6

1Institut für Physikalische Biologie and BMFZ, Heinrich-Heine-Universität Düsseldorf, Universitätsstraße 1, D-40225 Düsseldorf, Germany and Institut für Neurowissenschaften und Biophysik INB-2, Forschungszentrum Jülich, D-52425 Jülich, Germany
The first two authors contributed equally to this work.

2Institut für Physikalische Biologie and BMFZ, Heinrich-Heine-Universität Düsseldorf, Universitätsstraße 1, D-40225 Düsseldorf, Germany, Institut für Neurowissenschaften und Biophysik INB-2, Forschungszentrum Jülich, D-52425 Jülich, Germany and Present address: Institut für Biochemie, Westfälische Wilhelms-Universität Münster, Wilhelm-Klemm-Str. 2, D-48149 Münster, Germany.

3Institut für Physikalische Biologie and BMFZ, Heinrich-Heine-Universität Düsseldorf, Universitätsstraße 1, D-40225 Düsseldorf, Germany and Institut für Neurowissenschaften und Biophysik INB-2, Forschungszentrum Jülich, D-52425 Jülich, Germany

4Institut für Physikalische Biologie and BMFZ, Heinrich-Heine-Universität Düsseldorf, Universitätsstraße 1, D-40225 Düsseldorf, Germany and Institut für Neurowissenschaften und Biophysik INB-2, Forschungszentrum Jülich, D-52425 Jülich, Germany

5Institut für Physikalische Biologie and BMFZ, Heinrich-Heine-Universität Düsseldorf, Universitätsstraße 1, D-40225 Düsseldorf, Germany and Institut für Neurowissenschaften und Biophysik INB-2, Forschungszentrum Jülich, D-52425 Jülich, Germany

6Institut für Physikalische Biologie and BMFZ, Heinrich-Heine-Universität Düsseldorf, Universitätsstraße 1, D-40225 Düsseldorf, Germany and Institut für Neurowissenschaften und Biophysik INB-2, Forschungszentrum Jülich, D-52425 Jülich, Germany

Corresponding author

Citation Information: Biological Chemistry. Volume 388, Issue 6, Pages 611–615, ISSN (Online) 14316730, ISSN (Print) 14374315, DOI: 10.1515/BC.2007.075, June 2007

Publication History

Received:
2007-01-26
Accepted:
2007-03-20
Published Online:
2007-06-01

Abstract

We studied the interaction of the artificial 12-aa proline-rich peptide PD1 with the SH3 domain of the hematopoietic cell kinase Hck and the peptide's potency in competitively displacing HIV-1 Nef from the Hck SH3 domain. PD1 was obtained from a phage display screen and exhibits exceptional affinity for the Hck SH3 domain (K d=0.23 μM). Competition experiments using NMR spectroscopy demonstrate that the peptide even displaces Nef from Hck SH3 and allow for estimation of the Nef-Hck SH3 dissociation constant (K d=0.44 μM), the strongest SH3 ligand interaction known so far. Consequences of this study for novel antiviral concepts are discussed.

Keywords: competition; Hck; HIV; Nef; NMR; protein-peptide interaction; SH3

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