title: Structural basis of SH2 domain mutations in X-linked agammaglobulinemia.
abstract: The three-dimensional structure of Bruton's agammaglobulinemia tyrosine kinase (Btk) SH2 domain was modeled based on v-Src. Btk SH2 is presumably very related to the other SH2 structures consisting of two beta-sheets surrounded by two alpha-helices, with a well conserved hydrophobic core and phoshotyrosyl peptide binding site. The model was used to predict the recognition sequence of the target protein, which probably is YEXI/L. Mutations in the Btk sequence can cause the human disease X-linked agammaglobulinemia and reasons for the disease in Btk SH2 mutations were inferred from the model.
authors.affiliation: Center for Structural Biochemistry, Karolinska Institute, NOVUM, Huddinge, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Vihinen
authors.forename: L
authors.initials: L
authors.lastname: Nilsson
authors.forename: C I
authors.initials: CI
authors.lastname: Smith
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000235:genetics*; D000595:Amino Acid Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D004251:DNA Transposable Elements; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015688:Oncogene Protein pp60(v-src) / Q000737:chemistry; D019000:Phosphotyrosine; D017354:Point Mutation; D017433:Protein Structure, Secondary; D011505:Protein-Tyrosine Kinases / Q000737:chemistry* / Q000235:genetics*; D017384:Sequence Deletion; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014960:X Chromosome
chemical_list: D004251:DNA Transposable Elements; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; D015688:Oncogene Protein pp60(v-src)