title: Probing muscle myosin motor action: x-ray (m3 and m6) interference measurements report motor domain not lever arm movement.
abstract: The key question in understanding how force and movement are produced in muscle concerns the nature of the cyclic interaction of myosin molecules with actin filaments. The lever arm of the globular head of each myosin molecule is thought in some way to swing axially on the actin-attached motor domain, thus propelling the actin filament past the myosin filament. Recent X-ray diffraction studies of vertebrate muscle, especially those involving the analysis of interference effects between myosin head arrays in the two halves of the thick filaments, have been claimed to prove that the lever arm moves at the same time as the sliding of actin and myosin filaments in response to muscle length or force steps. It was suggested that the sliding of myosin and actin filaments, the level of force produced and the lever arm angle are all directly coupled and that other models of lever arm movement will not fit the X-ray data. Here, we show that, in addition to interference across the A-band, which must be occurring, the observed meridional M3 and M6 X-ray intensity changes can all be explained very well by the changing diffraction effects during filament sliding caused by heads stereospecifically attached to actin moving axially relative to a population of detached or non-stereospecifically attached heads that remain fixed in position relative to the myosin filament backbone. Crucially, and contrary to previous interpretations, the X-ray interference results provide little direct information about the position of the myosin head lever arm; they are, in fact, reporting relative motor domain movements. The implications of the new interpretation are briefly assessed.
authors.affiliation: Cardiff University, UK.
authors.forename: Carlo
authors.initials: C
authors.lastname: Knupp
authors.forename: Gerald
authors.initials: G
authors.lastname: Offer
authors.forename: K W
authors.initials: KW
authors.lastname: Ranatunga
authors.forename: John M
authors.initials: JM
authors.lastname: Squire
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D009068:Movement; D009119:Muscle Contraction / Q000502:physiology*; D009218:Myosins / Q000737:chemistry* / Q000378:metabolism*; D053838:Scattering, Small Angle
chemical_list: D009218:Myosins