title: Structural basis for specific binding of the Gads SH3 domain to an RxxK motif-containing SLP-76 peptide: a novel mode of peptide recognition.
abstract: The SH3 domain, which normally recognizes proline-rich sequences, has the potential to bind motifs with an RxxK consensus. To explore this novel specificity, we have determined the solution structure of the Gads T cell adaptor C-terminal SH3 domain in complex with an RSTK-containing peptide, representing its physiological binding site on the SLP-76 docking protein. The SLP-76 peptide engages four distinct binding pockets on the surface of the Gads SH3 domain and upon binding adopts a unique structure characterized by a right-handed 3(10) helix at the RSTK locus, in contrast to the left-handed polyproline type II helix formed by canonical proline-rich SH3 ligands. The structure, and supporting mutagenesis and peptide binding data, reveal a novel mode of ligand recognition by SH3 domains.
authors.affiliation: Department of Biochemistry, Faculty of Medicine and Dentistry, University of Western Ontario, N6A 5C1, London, Ontario, Canada.
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
authors.forename: Donna
authors.initials: D
authors.lastname: Berry
authors.forename: Piers
authors.initials: P
authors.lastname: Nash
authors.forename: Tony
authors.initials: T
authors.lastname: Pawson
authors.forename: C Jane
authors.initials: CJ
authors.lastname: McGlade
authors.forename: Shawn Shun-Cheng
authors.initials: SS
authors.lastname: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D019169:Jurkat Cells; D008024:Ligands; D046911:Macromolecular Substances; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D010750:Phosphoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011392:Proline / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055672:Static Electricity; D018909:src Homology Domains / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C409587:GRAP2 protein, human; D008024:Ligands; D046911:Macromolecular Substances; D010750:Phosphoproteins; D011994:Recombinant Proteins; C092947:SLP-76 signal Transducing adaptor proteins; D011392:Proline