STRUCTURAL BASES OF REGULATION OF SKELETAL MUSCLE

The dual regulation of muscle contraction provides that, beyond the classical Ca2+ dependent thin filament activation that makes the actin available for interaction with myosin motors, thick filament mechano-sensing switches ON the motors from the energetically convenient OFF state in relation to the load. Evidence is growing for the involvement in thick filament regulation of sarcomere proteins: titin, which runs from the midpoint of the thick filament to its tip and then extends from there to the end of the sarcomere, and the myosin binding protein C (MyBP-C), which is bound to the backbone of the thick filament in the central one-third and bridges thin filaments. Our research is aimed at verifying MyBP-C role in inter-filament communication and titin role in thick filament mechanosensing. The planned experiments, conducted in intact skeletal muscle fibres, are based on the recent finding that X-ray fine structure of thick filament reports the footprints of both MyBP-C and titin.