title: Steric-blocking by tropomyosin visualized in relaxed vertebrate muscle thin filaments.
abstract: Although widely accepted, the steric-blocking model of vertebrate skeletal muscle regulation has not been confirmed. Previous attempts to directly visualize tropomyosin in relaxed skeletal muscle and demonstrate that it interferes with the crossbridge-thin filament contractile cycle were unsuccessful. In the work reported here, tropomyosin was resolved in electron micrographs of native thin filaments isolated from relaxed vertebrate striated muscle. Three-dimensional helical reconstructions of these filaments showed continuous narrow strands of density, representing tropomyosin, which followed the outer domains of successive actin monomers. The results obtained from fitting the atomic model of filamentous actin to these reconstructions illustrate, and are consistent with, the mechanism of steric-blocking, since tropomyosin was found to be positioned on the actin surface of thin filaments over clusters of identifiable amino acids required for myosin crossbridge docking.
authors.affiliation: Department of Physiology, Boston University School of Medicine, Massachusetts 02118, USA.
authors.forename: W
authors.initials: W
authors.lastname: Lehman
authors.forename: P
authors.initials: P
authors.lastname: Vibert
authors.forename: P
authors.initials: P
authors.lastname: Uman
authors.forename: R
authors.initials: R
authors.lastname: Craig
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry / Q000648:ultrastructure*; D000199:Actins / Q000737:chemistry / Q000648:ultrastructure; D000818:Animals; D003196:Computer Graphics; D004591:Electrophoresis, Polyacrylamide Gel; D005583:Fourier Analysis; D008854:Microscopy, Electron; D008958:Models, Molecular; D009126:Muscle Relaxation / Q000502:physiology*; D018482:Muscle, Skeletal / Q000737:chemistry; D009206:Myocardium / Q000737:chemistry; D009210:Myofibrils / Q000737:chemistry; D011892:Rana catesbeiana; D011894:Rana pipiens; D014335:Tropomyosin / Q000737:chemistry*
chemical_list: D000199:Actins; D014335:Tropomyosin