Native DGC structure rationalizes muscular dystrophy-causing mutations.

ABSTRACT: Duchenne muscular dystrophy (DMD) is a severe X-linked recessive disorder marked by progressive muscle wasting leading to premature mortality^1,2. Discovery of the DMD gene encoding dystrophin both revealed the cause of DMD and helped identify a family of at least ten dystrophin-associated proteins at the muscle cell membrane, collectively forming the dystrophin-glycoprotein complex (DGC)^3-9. The DGC links the extracellular matrix to the cytoskeleton, but, despite its importance, its molecular architecture has remained elusive. Here we determined the native cryo-electron microscopy structure of rabbit DGC and conducted biochemical analyses to reveal its intricate molecular configuration. An unexpected β-helix comprising β-, γ- and δ-sarcoglycan forms an extracellular p

SUBMITTER: Liu S 

PROVIDER: S-EPMC11936492 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature