spacer Structural analysis of the yeast actin binding protein Abp1 SH3 domain
Primary citation
Title Unusual binding properties of the SH3 domain of the yeast actin-binding protein Abp1: structural and functional analysis.
Authors Fazi,; Cope,; Douangamath,; Ferracuti,; Schirwitz,; Zucconi,; Drubin,; Wilmanns,; Cesareni,; Castagnoli,
Journal vol:277, pag:5290-5298 (2002), Identifiers: PubMed ID (11668184)search DOI (10.1074/jbc.M109848200)
Abstract Abp1p is an actin-binding protein that plays a central role in the organization of Saccharomyces cerevisiae actin cytoskeleton. By a combination of two-hybrid and phage-display approaches, we have identified six new ligands of the Abp1-SH3 domain. None of these SH3-mediated novel interactions was detected in recent all genome high throughput protein interaction projects. Here we show that the SH3-mediated association of Abp1p with the Ser/Thr kinases Prk1p and Ark1p is essential for their localization to actin cortical patches. The Abp1-SH3 domain has a rather unusual binding specificity, because its target peptides contain the tetrapentapeptide +XXXPXXPX+PXXL with positive charges flanking the polyproline core on both sides. Here we present the structure of the Abp1-SH3 domain solved at 1.3-A resolution. The peptide-binding pockets in the SH3 domain are flanked by two acidic residues that are uncommon at those positions in the SH3 domain family. We have shown by site-directed mutagenesis that one of these negatively charged side chains may be the key determinant for the preference for non-classical ligands.
MeSH terms Actinssearch, Amino Acid Motifssearch, Amino Acid Sequencesearch, Binding Sitessearch, Cytoskeletonsearch, DNA-Binding Proteinssearch, Endocytosissearch, Enzyme-Linked Immunosorbent Assaysearch, Gene Librarysearch, Ligandssearch, Modelssearch, Biologicalsearch, Modelssearch, Molecularsearch, Molecular Sequence Datasearch, Mutagenesissearch, Site-Directedsearch, Peptide Librarysearch, Peptidessearch, Plant Proteinssearch, Plasmidssearch, Protein Bindingsearch, Protein Conformationsearch, Protein Structuresearch, Tertiarysearch, Receptor Protein-Tyrosine Kinasessearch, Saccharomyces cerevisiaesearch, Saccharomyces cerevisiae Proteinssearch, Schizosaccharomyces pombe Proteinssearch, Structure-Activity Relationshipsearch, Transcription Factorssearch, Two-Hybrid System Techniquessearch, src Homology Domainssearch