title: Solution structure of the Shc SH2 domain complexed with a tyrosine-phosphorylated peptide from the T-cell receptor.
abstract: She is a widely expressed adapter protein that plays an important role in signaling via a variety of cell surface receptors and has been implicated in coupling the stimulation of growth factor, cytokine, and antigen receptors to the Ras signaling pathway. She interacts with several tyrosine-phosphorylated receptors through its C-terminal SH2 domain, and one of the mechanisms of T-cell receptor-mediated Ras activation involves the interaction of the Shc SH2 domain with the tyrosine-phosphorylated zeta chain of the T-cell receptor. Here we describe a high-resolution NMR structure of the Shc SH2 domain complexed to a phosphopeptide (GHDGLpYQGLSTATK) corresponding to a portion of the zeta chain of the T-cell receptor. Although the overall architecture of the protein is similar to other SH2 domains, distinct structural differences were observed in the smaller beta-sheet, BG loop, (pY + 3) phosphopeptide-binding site, and relative position of the bound phosphopeptide.
authors.affiliation: Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, IL 60064 USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Zhou
authors.forename: R P
authors.initials: RP
authors.lastname: Meadows
authors.forename: T M
authors.initials: TM
authors.lastname: Logan
authors.forename: H S
authors.initials: HS
authors.lastname: Yoon
authors.forename: W S
authors.initials: WS
authors.lastname: Wade
authors.forename: K S
authors.initials: KS
authors.lastname: Ravichandran
authors.forename: S J
authors.initials: SJ
authors.lastname: Burakoff
authors.forename: S W
authors.initials: SW
authors.lastname: Fesik
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003001:Cloning, Molecular; D017124:Conserved Sequence; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification; D010748:Phosphopeptides / Q000737:chemistry / Q000302:isolation & purification; D010766:Phosphorylation; D019000:Phosphotyrosine; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D055765:Shc Signaling Adaptor Proteins; D012996:Solutions; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D010446:Peptide Fragments; D010748:Phosphopeptides; D011506:Proteins; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D055765:Shc Signaling Adaptor Proteins; D012996:Solutions; D019000:Phosphotyrosine; D014443:Tyrosine