The "roll and lock" mechanism of force generation in muscle.
Muscle force results from the interaction of the globular heads of myosin-II with actin filaments. We studied the structure-function relationship in the myosin motor in contracting muscle fibers by using temperature jumps or length steps combined with time-resolved, low-angle X-ray diffraction. Both perturbations induced simultaneous changes in the active muscle force and in the extent of labeling of the actin helix by stereo-specifically bound myosin heads at a constant total number of attached heads. The generally accepted hypothesis assumes that muscle force is generated solely by tilting of the lever arm, or the light chain domain of the myosin head, about its catalytic domain firmly bound to actin. Data obtained suggest an additional force-generating step: the "roll and lock" transition of catalytic domains of non-stereo-specifically attached heads to a stereo-specifically bound state. A model based on this scheme is described to quantitatively explain the data.
Ferenczi
Michael A
MA
Imperial College, London SW7 2AZ, UK. m.ferenczi@imperial.ac.uk
Bershitsky
Sergey Y
SY
Koubassova
Natalia
N
Siththanandan
Verl
V
Helsby
William I
WI
Panine
Pierre
P
Roessle
Manfred
M
Narayanan
Theyencheri
T
Tsaturyan
Andrey K
AK
D000199:Actins / Q000737:chemistry / Q000502:physiology; D000818:Animals; D001696:Biomechanical Phenomena; D020134:Catalytic Domain; D007700:Kinetics; D008954:Models, Biological; D008958:Models, Molecular; D008961:Models, Structural; D009119:Muscle Contraction; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology*; D009218:Myosins / Q000737:chemistry / Q000502:physiology; D017434:Protein Structure, Tertiary; D011817:Rabbits; D013696:Temperature; D014961:X-Ray Diffraction
D000199:Actins; D009218:Myosins