Conformation of the myosin motor during force generation in skeletal muscle.
Myosin motors drive muscle contraction, cytokinesis and cell locomotion, and members of the myosin superfamily have been implicated in an increasingly diverse range of cell functions. Myosin can displace a bound actin filament several nanometers in a single interaction. Crystallographic studies suggest that this 'working stroke' involves bending of the myosin head between its light chain and catalytic domains. Here we used X-ray fiber diffraction to test the crystallographic model and measure the interdomain bending during force generation in an intact single muscle fiber. The observed bending has two components: an elastic distortion and an active rotation that generates force. The average bend of the force-generating myosin heads in a muscle fiber is intermediate between those in crystal structures with different bound nucleotides, and the C-terminus of the head is displaced by 7 nm along the actin filament axis compared with the in vitro conformation seen in the absence of nucleotide.
Irving
M
M
School of Biomedical Sciences, King's College London, London, UK. malcolm.irving@kcl.ac.uk
Piazzesi
G
G
Lucii
L
L
Sun
Y B
YB
Harford
J J
JJ
Dobbie
I M
IM
Ferenczi
M A
MA
Reconditi
M
M
Lombardi
V
V
D000199:Actins / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001704:Biopolymers / Q000737:chemistry / Q000378:metabolism; D020134:Catalytic Domain; D004548:Elasticity; D004558:Electric Stimulation; D007537:Isometric Contraction; D007700:Kinetics; D008954:Models, Biological; D008958:Models, Molecular; D020409:Molecular Motor Proteins / Q000737:chemistry / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D018482:Muscle, Skeletal / Q000737:chemistry* / Q000166:cytology / Q000502:physiology*; D009218:Myosins / Q000737:chemistry* / Q000378:metabolism*; D009711:Nucleotides / Q000378:metabolism; D011487:Protein Conformation; D011896:Rana temporaria; D012399:Rotation; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
D000199:Actins; D001704:Biopolymers; D020409:Molecular Motor Proteins; D009711:Nucleotides; D009218:Myosins