The Structure of the N-terminal Region of Murine Skeletal Muscle α-Dystroglycan Discloses a Modular Architecture

• DOI: 10.1074/jbc.c400353200
• Publication Date: 2004-08-24T00:12:50Z
• Authors: Damir Bozic; Francesca Sciandra; Doriano Lamba; Andrea Brancaccio
• Keywords: Models, Molecular; 0301 basic medicine; Protein Conformation; Muscle Fibers, Skeletal; Electrons; Cell Biology; Crystallography, X-Ray; Biochemistry; Recombinant Proteins; Protein Structure, Tertiary; Mice; 03 medical and health sciences; Animals; RNA; Biotinylation; Laminin; Dystroglycans; Muscle, Skeletal; Molecular Biology; Software; Protein Binding

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-A 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.