Structural Basis of Muscle Regulation by Synchrotron X-ray Diffraction— Head-Head Interactions of Myosin Crossbridges in Resting Higher Vertebrate Striated Muscle

Abstract

Skeletal muscle contraction is regulated mainly by Ca²⁺ binding to the thin actin filaments in a sarcomere, but the participation of the thick myosin filament in the regulatory mechanism has remained to be clarified. The lattice sampling-free intensities of the myosin layer lines in the X-ray diffraction patterns from live resting higher vertebrate striated muscles with a full thick-thin filament overlap were analyzed. Atomic modeling of the myosin filament was performed, revealing the head-head interactions of myosin crossbridges, which are in common among various resting striated muscles. The head-head interactions are primarily electrostatic and the converter domain is responsible for their interactions. The results indicate that multiple head-head interactions of myosin crossbridges stabilize the resting myosin structure and play a role in the regulatory function also in the thin filament-regulated muscles.