X-ray structure of the SH3 domain of the phosphoinositide 3-kinase p85β subunit

Src-homology 3 (SH3) domains are involved in extensive protein-protein interactions and constitute key elements of intracellular signal transduction. Three-dimensional structures have been reported for SH3 domains of various proteins, including the 85 kDa regulatory subunit (p85) of phosphoinositide 3-kinase. However, all of the latter structures are of p85 isoform alpha and no crystal structure of the SH3 domain of the equally important isoform beta has been reported to date. In this structural communication, the recombinant production, crystallization and X-ray structure determination at 2.0 angstrom resolution of the SH3 domain of human p85 beta is described. The structure reveals a compact beta-barrel fold very similar to that of p85 alpha. However, binding studies with two classes of proline-rich ligand peptides demonstrate that the ligand-binding specificity differs slightly between the SH3 domains of human p85 beta and p85 alpha, despite their high structural similarity.