title: Competitive displacement of full-length HIV-1 Nef from the Hck SH3 domain by a high-affinity artificial peptide.
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 microM). 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 microM), the strongest SH3 ligand interaction known so far. Consequences of this study for novel antiviral concepts are discussed.
authors.affiliation: Institut für Physikalische Biologie and BMFZ, Heinrich-Heine-Universität Düsseldorf, Universitätsstrasse 1, D-40225 Düsseldorf, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Stangler
authors.forename: Tuyen
authors.initials: T
authors.lastname: Tran
authors.forename: Silke
authors.initials: S
authors.lastname: Hoffmann
authors.forename: Holger
authors.initials: H
authors.lastname: Schmidt
authors.forename: Esther
authors.initials: E
authors.lastname: Jonas
authors.forename: Dieter
authors.initials: D
authors.lastname: Willbold
mesh_terms: D001667:Binding, Competitive; D015693:Gene Products, nef / Q000378:metabolism*; D006801:Humans; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding; D051572:Proto-Oncogene Proteins c-hck / Q000378:metabolism*; D054311:nef Gene Products, Human Immunodeficiency Virus; D018909:src Homology Domains
chemical_list: D015693:Gene Products, nef; D010455:Peptides; D054311:nef Gene Products, Human Immunodeficiency Virus; C496631:HCK protein, human; D051572:Proto-Oncogene Proteins c-hck