title: Structural basis for IL-4 receptor phosphopeptide recognition by the IRS-1 PTB domain.
abstract: We present the NMR structure of the PTB domain of insulin receptor substrate-1 (IRS-1) complexed to a tyrosine-phosphorylated peptide derived from the IL-4 receptor. Despite the lack of sequence homology and different binding specificity, the overall fold of the protein is similar to that of the Shc PTB domain and closely resembles that of PH domains. However, the PTB domain of IRS-1 is smaller than that of Shc (110 versus 170 residues) and binds to phosphopeptides in a distinct manner. We explain the phosphopeptide binding specificity based on the structure of the complex and results of site-directed mutagenesis experiments.
authors.affiliation: Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, Illinois 60064, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Zhou
authors.forename: B
authors.initials: B
authors.lastname: Huang
authors.forename: E T
authors.initials: ET
authors.lastname: Olejniczak
authors.forename: R P
authors.initials: RP
authors.lastname: Meadows
authors.forename: S B
authors.initials: SB
authors.lastname: Shuker
authors.forename: M
authors.initials: M
authors.lastname: Miyazaki
authors.forename: T
authors.initials: T
authors.lastname: Trüb
authors.forename: S E
authors.initials: SE
authors.lastname: Shoelson
authors.forename: S W
authors.initials: SW
authors.lastname: Fesik
mesh_terms: D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D055504:Insulin Receptor Substrate Proteins; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010748:Phosphopeptides / Q000737:chemistry* / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019000:Phosphotyrosine / Q000378:metabolism; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D018123:Receptors, Interleukin / Q000737:chemistry* / Q000378:metabolism; D019948:Receptors, Interleukin-4; D016415:Sequence Alignment
chemical_list: D015703:Antigens, CD; D055504:Insulin Receptor Substrate Proteins; D010748:Phosphopeptides; D010750:Phosphoproteins; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D019000:Phosphotyrosine