Structure of a WW domain containing fragment of dystrophin in complex withbeta-dystroglycan

Dystrophin and beta-dystroglycan are components of the dystrophin-glcoprote in complex (DGC), a multimolecular assembly that spans the cell membrane an d links the actin cytoskeleton to the extracellular basal lamina. Defects i n the dystrophin gene are the cause of Duchenne and pecker muscular dystrop hies. The C-terminal region of dystrophin binds the cytoplasmic tail of bet a-dystroglycan, in part through the interaction of its WW domain with a pro line-rich moth in the tail of beta-dystroglycan. Here we report the crystal structure of this portion of dystrophin in complex with the proline-rich b inding site in beta-dystroglycan. The structure shows that the dystrophin W W domain is embedded in an adjacent helical region that contains two EF-han d-like domains. The beta-dystroglycan peptide binds a composite surface for med by the WW domain and one of these EF-hands. Additionally, the structure reveals striking similarities in the mechanisms of proline recognition emp loyed by WW domains and SH3 domains.