ナノメディシンとナノテクノロジーのジャーナル

概要

Evidence for the Regulation of Actin-myosin Binding Strength by Lever Arm and Subfragment-2 Regions of Myosin Molecule in Contracting Skinned Muscle Fibers as Revealed by the Effect of Antibodies

Sugi H and Chaen S

It is generally believed that myosin heads (M) extending from myosin filaments form weak binding with actin filament (A) in the form of A-M-ADP-Pi, and strong binding with A in the form of A-M-ADP and A-M. During muscle contraction, M first attaches weakly to A in the form of M-ADP-Pi, and then release Pi to attach strongly with A in the form of A-MADP to exert power stroke producing myofilament sliding. The weak to strong binding transition between M and A is therefore essential for producing muscle contraction. After power stroke, associated with release of ADP, M detaches from A on binding with next ATP to form M-ADP-Pi. Thus, M repeats attachment-detachment cycle with A, coupled with ATP hydrolysis. Using antibodies to myosin lever arm domain (anti-LD antibody) and to myosin subfragment-2 region (anti-S-2 antibody), we have found that, if these antibodies attach to LD or S-2 regions, myosin heads no longer generate force, but still hydrolyse ATP at a normal rate without contributing to muscle fiber stiffness and internal resistance against fiber shortening. The puzzling effect of antibodies can be accounted for by assuming that in myosin molecules, with antibodies attached to their LD or S-2 region, (1) the strength of A-M binding is markedly reduced to be readily broken by small length perturbations or muscle fiber shortening, and (2) such myosin heads still repeat attachmentdetachment cycle coupled with ATP hydrolysis without passing through weak to strong A-M binding transition. Thus, the present work indicates functional influence of LD and S-2 regions on the A-M binding of myosin molecule, suggesting essential role of these regions in muscle contraction.