title: High-resolution crystal structures of tyrosine kinase SH3 domains complexed with proline-rich peptides.
abstract: Src-homology 3 (SH3) domains bind to proline-rich motifs in target proteins. We have determined high-resolution crystal structures of the complexes between the SH3 domains of Abl and Fyn tyrosine kinases, and two ten-residue proline-rich peptides derived from the SH3-binding proteins 3BP-1 and 3BP-2. The X-ray data show that the basic mode of binding of both proline-rich peptides is the same. Peptides are bound over their entire length and interact with three major sites on the SH3 molecules by both hydrogen-bonding and van der Waals contacts. Residues 4-10 of the peptide adopt the conformation of a left-handed polyproline helix type II. Binding of the proline at position 2 requires a kink at the non-proline position 3.
authors.affiliation: European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Musacchio
authors.forename: M
authors.initials: M
authors.lastname: Saraste
authors.forename: M
authors.initials: M
authors.lastname: Wilmanns
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D018360:Crystallography, X-Ray; D006801:Humans; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism*; D011392:Proline / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000378:metabolism*; D016315:Proto-Oncogene Proteins c-abl / Q000737:chemistry* / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
chemical_list: D010455:Peptides; D011518:Proto-Oncogene Proteins; D011392:Proline; C494957:FYN protein, human; D016315:Proto-Oncogene Proteins c-abl; D051076:Proto-Oncogene Proteins c-fyn