title: Crystal structure of the PI 3-kinase p85 amino-terminal SH2 domain and its phosphopeptide complexes.
abstract: Crystal structures of the amino-terminal SH2 domain of the p85alpha subunit of phosphatidylinositol (PI) 3-kinase, alone and in complex with phosphopeptides bearing pTyr-Met/Val-Xaa-Met motifs, show that phosphopeptides bind in the two-pronged manner seen in high-affinity Lck and Src SH2 complexes, with conserved interactions between the domain and the peptide segment from phosphotyrosine to Met+3. Peptide binding requires the rearrangement of a tyrosyl side chain in the BG loop to create the hydrophobic Met+3 binding pocket. The structures suggest a mechanism for the biological specificity exhibited by PI 3-kinase in its interactions with phosphoprotein partners.
authors.affiliation: Howard Hughes Medical Institute and Laboratory of Molecular Medicine, Children's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: R T
authors.initials: RT
authors.lastname: Nolte
authors.forename: M J
authors.initials: MJ
authors.lastname: Eck
authors.forename: J
authors.initials: J
authors.lastname: Schlessinger
authors.forename: S E
authors.initials: SE
authors.lastname: Shoelson
authors.forename: S C
authors.initials: SC
authors.lastname: Harrison
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D008715:Methionine / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases; D010748:Phosphopeptides / Q000737:chemistry* / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D019009:Proto-Oncogene Proteins c-kit / Q000737:chemistry; D017479:Receptors, Platelet-Derived Growth Factor / Q000737:chemistry; D018909:src Homology Domains
chemical_list: D010748:Phosphopeptides; D008715:Methionine; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D019009:Proto-Oncogene Proteins c-kit; D017479:Receptors, Platelet-Derived Growth Factor