Structural basis of SH2 domain mutations in X-linked agammaglobulinemia

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.