Three-Dimensional Structural Analysis of Individual Myosin Heads Under Various Functional States

摘要: Half a century has passed since the dedicated studies on contraction mechanisms of muscle began, with considerable knowledge its molecular architecture. Two major hypotheses were raised very early, one, ”sliding filament theory”,1,2 and other, “crossbridge theory”. 3 The former was readily accepted, because phenomenon apparently visible under optical microscope. latter, however, been hindered from thorough experimental proof even now, though nothing other than crossbridges connect thick thin filaments enabling force development. original idea postulated rowing movement actin-bound myosin head coupled ATP hydrolysis, but it later replaced by swinging “lever-arm” moiety,4 according to discovery intramolecular bending X-ray crystallography.5-8 One reasons for such persistent difficulty prove this simple hypothesis might be lack means directly observe actual structural change working time spatial resolution enough visualize fine details nano-machine. Though crystal structure each component; actin9, 10 subfragment-1 (S1) or without various nucleotides,5-8 determined ten years ago, none their complexed form solved nor subject matter easy crystallization.