title: Cooperative [Ca²+]-dependent regulation of the rate of myosin binding to actin: solution data and the tropomyosin chain model.
abstract: The regulation of muscle contraction by calcium involves interactions among actin filaments, myosin-S1, tropomyosin (Tm), and troponin (Tn). We have extended our previous model in which the TmTn regulatory units are treated as a continuous flexible chain, and applied it to transient kinetic data. We have measured the time course of myosin-S1 binding to actin-Tm-Tn filaments in solution at various calcium levels with [actin]/[myosin] ratios of 10 and 0.1, which exhibit modest slowing as [Ca(2+)] is reduced and a lag phase at low calcium. These observations can be explained if myosin binds to actin in two steps, where the first step is rate-limiting and blocked by TmTnI at low calcium, and the second step is fast, reversible, and controlled by the neighboring configuration of coupled tropomyosin-troponin units. The model can describe the calcium dependence of the observed myosin binding reactions and predicts cooperative calcium binding to TnC with competition between actin and Ca-TnC for the binding of TnI. Implications for theories of thin-filament regulation in muscle are discussed.
authors.affiliation: Department of Biosciences, University of Kent, Canterbury, Kent, United Kingdom. m.a.geeves@kent.ac.uk
authors.forename: Michael
authors.initials: M
authors.lastname: Geeves
authors.forename: Hugh
authors.initials: H
authors.lastname: Griffiths
authors.forename: Srboljub
authors.initials: S
authors.lastname: Mijailovich
authors.forename: David
authors.initials: D
authors.lastname: Smith
mesh_terms: D000199:Actins / Q000378:metabolism*; D000494:Allosteric Regulation; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D007700:Kinetics; D008954:Models, Biological; D009010:Monte Carlo Method; D009218:Myosins / Q000378:metabolism*; D011485:Protein Binding; D011817:Rabbits; D012996:Solutions; D014335:Tropomyosin / Q000737:chemistry* / Q000378:metabolism*; D019210:Troponin I / Q000378:metabolism
chemical_list: D000199:Actins; D012996:Solutions; D014335:Tropomyosin; D019210:Troponin I; D009218:Myosins; D002118:Calcium