Is the Myosin Head Conformation Coupled to the Thick Filament Backbone Structure?

Abstract

Some striated muscles thick filaments show evidence of structural changes in response to activation or tension. Relaxed thick filaments from Lethocerus flight muscle change their helical angle by −0.15°/crown (145Å repeat) in response to externally applied tension. The change in helical angle, which is a structural parameter defined by the myosin rods within the filament backbone, is accompanied by intensity changes in the 145Å layer line, which is sensitive to the arrangement and order of the myosin heads. The intensity change could indicate that putting the relaxed muscle under tension alters the order or arrangement of at least some of the myosin heads. Vertebrate striated muscle thick filaments, which are not helical, change their axial repeat from 143Å to 145Å, the latter being the axial spacing in Lethocerus thick filaments. We reasoned that if externally applied tension could change the helical angle and the myosin head arrangement, that relaxed Lethocerus thick filaments with partially disordered heads might display an altered helical angle coupled to changes in myosin head arrangement. The 3-D images obtained by cryoEM, provide the first structural evidence that the arrangement of myosin heads within the interacting heads motif is coupled to the structure of the thick filament backbone. We find that a −0.16° change in helical angle disorders the blocked head preferentially, which suggests a mechanism for how tension affects the dynamics of the myosin heads and their contribution to stretch activation and shortening deactivation. We suggest the blocked head preferentially binds the thin filament followed by the free head when the blocked head produces force. The shift in blocked head dynamics from ordered to disordered is achieved by tension applied by the antagonist muscle. Supported by NIH and AHA.