Visualizing myosin's power stroke in muscle contraction.
The long-standing swinging crossbridge or lever arm hypothesis for the motor action of myosin heads finds support in recent results from 3-D tomograms of insect flight muscle (IFM) fast frozen during active contraction and from both fluorescence polarization and X-ray diffraction during rapid stretches or releases of isometrically contracting fibers. The latter provide direct evidence for lever arm movements synchronous with force changes. Rebuilding the atomic model of nucleotide-free subfragment 1 (S1) to fit fast-frozen, active IFM crossbridges suggests a two-stage power stroke in which the catalytic domain rolls on actin from weak to strong binding; this is followed by a 5-nm lever arm swing of the light chain domain, which gives a total interaction distance of approx. 12 nm. Comparison of S1 crystal structures with in situ myosin heads suggests that actin binding may be necessary in order to view the full repertoire of myosin motor action. The differing positions of the catalytic domains of actin-attached myosin heads in contracting IFM suggest that both the actin-myosin binding energy and the hydrolysis of ATP may be used to cock the crossbridge and drive the power stroke.
Reedy
M C
MC
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA. mary.reedy@cellbio.duke.edu
D008841:Actin Cytoskeleton / Q000737:chemistry / Q000502:physiology; D000199:Actins / Q000737:chemistry / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D017110:Freeze Substitution; D008958:Models, Molecular; D020409:Molecular Motor Proteins / Q000737:chemistry / Q000502:physiology*; D009119:Muscle Contraction; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000502:physiology; D018482:Muscle, Skeletal / Q000737:chemistry / Q000502:physiology*; D009218:Myosins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D011487:Protein Conformation; D014054:Tomography
D000199:Actins; D020409:Molecular Motor Proteins; D000255:Adenosine Triphosphate; D009218:Myosins