title: Conformation of the myosin motor during force generation in skeletal muscle.
abstract: 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.
authors.affiliation: School of Biomedical Sciences, King's College London, London, UK. malcolm.irving@kcl.ac.uk
authors.forename: M
authors.initials: M
authors.lastname: Irving
authors.forename: G
authors.initials: G
authors.lastname: Piazzesi
authors.forename: L
authors.initials: L
authors.lastname: Lucii
authors.forename: Y B
authors.initials: YB
authors.lastname: Sun
authors.forename: J J
authors.initials: JJ
authors.lastname: Harford
authors.forename: I M
authors.initials: IM
authors.lastname: Dobbie
authors.forename: M A
authors.initials: MA
authors.lastname: Ferenczi
authors.forename: M
authors.initials: M
authors.lastname: Reconditi
authors.forename: V
authors.initials: V
authors.lastname: Lombardi
mesh_terms: 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
chemical_list: D000199:Actins; D001704:Biopolymers; D020409:Molecular Motor Proteins; D009711:Nucleotides; D009218:Myosins