title: Cryo-EM structures of the actin:tropomyosin filament reveal the mechanism for the transition from C- to M-state.
abstract: Tropomyosin (Tm) is a key factor in the molecular mechanisms that regulate the binding of myosin motors to actin filaments (F-Actins) in most eukaryotic cells. This regulation is achieved by the azimuthal repositioning of Tm along the actin (Ac):Tm:troponin (Tn) thin filament to block or expose myosin binding sites on Ac. In striated muscle, including involuntary cardiac muscle, Tm regulates muscle contraction by coupling Ca(2+) binding to Tn with myosin binding to the thin filament. In smooth muscle, the switch is the posttranslational modification of the myosin. Depending on the activation state of Tn and the binding state of myosin, Tm can occupy the blocked, closed, or open position on Ac. Using native cryogenic 3DEM (three-dimensional electron microscopy), we have directly resolved and visualized cardiac and gizzard muscle Tm on filamentous Ac in the position that corresponds to the closed state. From the 8-Å-resolution structure of the reconstituted Ac:Tm filament formed with gizzard-derived Tm, we discuss two possible mechanisms for the transition from closed to open state and describe the role Tm plays in blocking myosin tight binding in the closed-state position.
authors.affiliation: Department of Biological Science and Institute of Molecular Biophysics, Florida State University, 91 Chieftan Way, Tallahassee, FL 32306, USA; Department of Physiology and Biophysics, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118-2526, USA.
authors.forename: Duncan R
authors.initials: DR
authors.lastname: Sousa
authors.forename: Scott M
authors.initials: SM
authors.lastname: Stagg
authors.forename: M Elizabeth
authors.initials: ME
authors.lastname: Stroupe
mesh_terms: D000199:Actins / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D000595:Amino Acid Sequence; D000818:Animals; D002645:Chickens; D020285:Cryoelectron Microscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009132:Muscles / Q000737:chemistry / Q000502:physiology; D009206:Myocardium / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D011817:Rabbits; D016415:Sequence Alignment; D014335:Tropomyosin / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D000199:Actins; D014335:Tropomyosin
keywords: 3DEM; Ac; F-Actin; HMW; PDB; Protein Data Bank; Tm; Tn; actin; actin filament; cryogenic 3DEM; cytoskeleton; high molecular weight; thin filament; three-dimensional electron microscopy; tropomyosin; troponin
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