title: Thin Filament Structure and the Steric Blocking Model.
abstract: By interacting with the troponin-tropomyosin complex on myofibrillar thin filaments, Ca2+ and myosin govern the regulatory switching processes influencing contractile activity of mammalian cardiac and skeletal muscles. A possible explanation of the roles played by Ca2+ and myosin emerged in the early 1970s when a compelling "steric model" began to gain traction as a likely mechanism accounting for muscle regulation. In its most simple form, the model holds that, under the control of Ca2+ binding to troponin and myosin binding to actin, tropomyosin strands running along thin filaments either block myosin-binding sites on actin when muscles are relaxed or move away from them when muscles are activated. Evidence for the steric model was initially based on interpretation of subtle changes observed in X-ray fiber diffraction patterns of intact skeletal muscle preparations. Over the past 25 years, electron microscopy coupled with three-dimensional reconstruction directly resolved thin filament organization under many experimental conditions and at increasingly higher resolution. At low-Ca2+, tropomyosin was shown to occupy a "blocked-state" position on the filament, and switched-on in a two-step process, involving first a movement of tropomyosin away from the majority of the myosin-binding site as Ca2+ binds to troponin and then a further movement to fully expose the site when small numbers of myosin heads bind to actin. In this contribution, basic information on Ca2+-regulation of muscle contraction is provided. A description is then given relating the voyage of discovery taken to arrive at the present understanding of the steric regulatory model.
authors.affiliation: Department of Physiology & Biophysics, Boston University School of Medicine, Boston, Massachusetts, U.S.A.
authors.forename: William
authors.initials: W
authors.lastname: Lehman
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry* / Q000378:metabolism; D000199:Actins / Q000737:chemistry / Q000378:metabolism; D000494:Allosteric Regulation; D000818:Animals; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D056004:Molecular Dynamics Simulation; D014335:Tropomyosin / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000199:Actins; D014335:Tropomyosin; D002118:Calcium