Research Project Specific Aims
(1) to accomplish a near-atomic description of the helical arrangement of myosin heads on the striated (tarantula) and cardiac (rabbit) thick filament surface, revealing the conformation and interactions between myosin heads which produces the relaxed state of myosin filaments.
(2) to unravel the structural basis of how myosin heads helices are established and maintained in the presence of ATP, by capturing the structural changes that occur when myosin helices are formed.
(3) to disclose the molecular details of the myosin-linked regulation that occurs through the mechanism of phosphorylation of the regulatory light chains of myosin, by capturing the structural changes that occur when myosin filaments are activated.
(4) to understand the importance of some mutations on the regulatory light chain which are associated with a phenotype of the hypertrophic cardiomyopathy.