Dystrophin, its interactions with other proteins, and implications for muscular dystrophy

Abstract

Duchenne muscular dystrophy is the most prevalent and severe form of human muscular dystrophy. Investigations into the molecular basis for Duchenne muscular dystrophy were greatly facilitated by seminal studies in the 1980s that identified the defective gene and its major protein product, dystrophin. Biochemical studies revealed its tight association with a multi-subunit complex, the so-named dystrophin-glycoprotein complex. Since its description, the dystrophin-glycoprotein complex has emerged as an important structural unit of muscle and also as a critical nexus for understanding a diverse array of muscular dystrophies arising from defects in several distinct genes. The dystrophin homologue utrophin can compensate at the cell/tissue level for dystrophin deficiency, but functions through distinct molecular mechanisms of protein-protein interaction.