Initiation of the power stroke in muscle: insights from the phosphate analog AlF4.
Motile forces in muscle are generated by the so-called "power stroke," a series of structural changes in the actomyosin cross-bridge driven by hydrolysis of ATP. The initiation of this power stroke is closely related to phosphate release after ATP cleavage and to the change of the myosin head from weak, nonstereospecific actin attachment to strong, stereospecific binding. The exact sequence of events, however, is highly controversial but crucial for the mechanism of how ATP hydrolysis drives structural changes in the head domain of myosins and related NTPases like kinesins and small G proteins. Here, we show that the phosphate analogue AlF4 can form two ADP.phosphate analog states, one with weak binding of myosin to actin and the other with strong binding of myosin to actin. Thus, change from weak to strong binding (i.e., the initiation of the power stroke) can occur before phosphate is released from the active site.
Kraft
Theresia
T
Department of Molecular and Cell Physiology, Medical School Hannover, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany.
Mählmann
Enke
E
Mattei
Thomas
T
Brenner
Bernhard
B
D000199:Actins / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D009119:Muscle Contraction / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D009218:Myosins / Q000378:metabolism*; D009942:Organometallic Compounds / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D011817:Rabbits; D014961:X-Ray Diffraction
D000199:Actins; D009942:Organometallic Compounds; D010710:Phosphates; C105164:adenosine diphosphate tetrafluoroaluminate; D000244:Adenosine Diphosphate; D009218:Myosins