title: Structural determinants of muscle thin filament cooperativity.
abstract: End-to-end connections between adjacent tropomyosin molecules along the muscle thin filament allow long-range conformational rearrangement of the multicomponent filament structure. This process is influenced by Ca(2+) and the troponin regulatory complexes, as well as by myosin crossbridge heads that bind to and activate the filament. Access of myosin crossbridges onto actin is gated by tropomyosin, and in the case of striated muscle filaments, troponin acts as a gatekeeper. The resulting tropomyosin-troponin-myosin on-off switching mechanism that controls muscle contractility is a complex cooperative and dynamic system with highly nonlinear behavior. Here, we review key information that leads us to view tropomyosin as central to the communication pathway that coordinates the multifaceted effectors that modulate and tune striated muscle contraction. We posit that an understanding of this communication pathway provides a framework for more in-depth mechanistic characterization of myopathy-associated mutational perturbations currently under investigation by many research groups.
authors.affiliation: Department of Biological Sciences, University of Massachusetts Lowell, One University Avenue, Lowell, MA 018154, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Moore
authors.affiliation: Department of Biomedical Engineering, Yale University, 55 Prospect Street, New Haven, CT 06511, USA.
authors.forename: Stuart G
authors.initials: SG
authors.lastname: Campbell
authors.affiliation: Department of Physiology & Biophysics, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, USA. Electronic address: wlehman@bu.edu.
authors.forename: William
authors.initials: W
authors.lastname: Lehman
mesh_terms: D000199:Actins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D006801:Humans; D009119:Muscle Contraction; D009132:Muscles / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D009218:Myosins / Q000378:metabolism; D014335:Tropomyosin / Q000378:metabolism
chemical_list: D000199:Actins; D014335:Tropomyosin; D009218:Myosins; D002118:Calcium
keywords: Actin; Cooperativity; Myosin; Thin filament; Tropomyosin; Troponin