The structure of the N-terminal region of murine skeletal muscle alpha-dystroglycan discloses a modular architecture

Dystroglycan (DG) is a cell surface receptor consisting of two subunits: {alpha}-dystroglycan, extracellular and highly glycosylated, and {beta}-dystroglycan, spanning the cell membrane. It is a pivotal member of the dystrophin-glycoprotein complex and is involved in a wide variety of important cellular processes such as the stabilization of the muscle fiber sarcolemma or the clustering of acetylcholine receptors. We report the 2.3-Å resolution crystal structure of the murine skeletal muscle N-terminal {alpha}-DG region, which confirms the presence of two autonomous domains; the first finally identified as an Ig-like and the second resembling ribosomal RNA-binding proteins. Solid-phase laminin binding assays show the occurrence of protein-protein type of interactions involving the Ig-like domain of {alpha}-DG.