Dynamics of Dystrophin's Actin-Binding Domain
Abstract
We have used pulsed electron paramagnetic resonance, calorimetry, and molecular dynamics simulations to examine the structural mechanism of binding for dystrophin's N-terminal actin-binding domain (ABD1) and compare it to utrophin's ABD1. Like other members of the spectrin superfamily, dystrophin's ABD1 consists of two calponin-homology (CH) domains, CH1 and CH2. Several mutations within dystrophin's ABD1 are associated with the development of severe degenerative muscle disorders Duchenne and Becker muscular dystrophies, highlighting the importance of understanding its structural biology. To investigate structural changes within dystrophin ABD1 upon binding to actin, we labeled the protein with spin probes and measured changes in inter-CH domain distance using double-electron electron resonance. Previous studies on the homologous protein utrophin showed that actin binding induces a complete structural opening of the CH domains, resulting in a highly ordered ABD1-actin complex. In this study, double-electron electron resonance shows that dystrophin ABD1 also undergoes a conformational opening upon binding F-actin, but this change is less complete and significantly more structurally disordered than observed for utrophin. Using mo...Continue Reading
References
A differential scanning calorimetric study of the thermal unfolding of apo- and holo-cytochrome b562
Binding of dystrophin's tandem calponin homology domain to F-actin is modulated by actin's structure
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Actin-binding Proteins
Actin-binding proteins are a component of the actin cytoskeleton that play essential roles in cellular functions such as regulation of actin polymerization, maintenance of cell polarity, gene expression regulation, cell motility and many more functions. Discover the latest research on actin-binding proteins here.