Study Highlights Critical Protein Interactions In Duchenne Muscular Dystrophy

A new study has shed light on the complex interactions between dystrophin, a protein critical to muscle stability, and its partner protein, dystrobrevin, offering new pathways for understanding and treating Duchenne Muscular Dystrophy (DMD). Published in the December issue of the Journal of Biological Chemistry, researchers characterize the mysterious C-terminal (CT) domain of dystrophin and its role in stabilizing cellular membranes across various tissues.

DMD, a severe genetic disorder that causes muscle weakness and shortens lifespans, arises from mutations in the gene encoding dystrophin. While current treatments can extend patients' lifespans, their high cost and limited efficacy underscore the urgent need for broader therapeutic approaches.

The study reveals that dystrophin's C-terminal domain interacts differently with the two major dystrobrevin isoforms, which bind to dystrophin. Variations in the amino acid composition of dystrobrevin proteins drive differences in binding affinity and interaction modes, influencing the stability of the dystrophin-associated protein complex across tissues, a key indication of DMD.

These findings offer a molecular explanation for the wide-ranging symptoms experienced by DMD patients, which extend beyond skeletal muscles to affect organs such as the heart and brain.

Reference: https://news.cuanschutz.edu/news-stories/new-study-uncovers-key-insights-into-protein-interactions-in-duchenne-muscular-dystrophy-paving-way-for-more-targeted-therapies