title: Structure of the PI3K SH3 domain and analysis of the SH3 family.
abstract: Src homology 3 (SH3) domains, which are found in many proteins involved in intracellular signal transduction, mediate specific protein-protein interactions. The three-dimensional structure of the SH3 domain in the p85 subunit of the phosphatidylinositol 3-kinase (PI3K) has been determined by multidimensional NMR methods. The molecule consists of four short helices, two beta turns, and two antiparallel beta sheets. The beta sheets are highly similar to corresponding regions in the SH3 domain of the tyrosine kinase Src, even though the sequence identity of the two domains is low. There is a unique 15 amino acid insert in PI3K that contains three short helices. There are substantial differences in the identity of the amino acids that make up the receptor site of SH3 domains. The results suggest that while the overall structures of the binding sites in the PI3K and Src SH3 domains are similar, their ligand binding properties may differ.
authors.affiliation: Department of Chemistry, Harvard University, Cambridge, Massachusetts 02138.
authors.forename: S
authors.initials: S
authors.lastname: Koyama
authors.forename: H
authors.initials: H
authors.lastname: Yu
authors.forename: D C
authors.initials: DC
authors.lastname: Dalgarno
authors.forename: T B
authors.initials: TB
authors.lastname: Shin
authors.forename: L D
authors.initials: LD
authors.lastname: Zydowsky
authors.forename: S L
authors.initials: SL
authors.lastname: Schreiber
mesh_terms: D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D006801:Humans; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D019869:Phosphatidylinositol 3-Kinases; D010770:Phosphotransferases / Q000737:chemistry / Q000648:ultrastructure*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000648:ultrastructure; D011994:Recombinant Proteins / Q000648:ultrastructure; D016415:Sequence Alignment; D015398:Signal Transduction; D013816:Thermodynamics
chemical_list: D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D010770:Phosphotransferases; D019869:Phosphatidylinositol 3-Kinases; D016392:Proto-Oncogene Proteins pp60(c-src)