Cooperative regulation of myosin-actin interactions by a continuous flexible chain II: actin-tropomyosin-troponin and regulation by calcium.
The model of myosin regulation by a continuous tropomyosin chain is generalized to a chain of tropomyosin-troponin units. Myosin binding to regulated actin is cooperative and initially inhibited by the chain as before. In the absence of calcium, myosin is further inhibited by the binding of troponin-I to actin, which through the whole of troponin pins the tropomyosin chain in a blocking position; myosin and TnI compete for actin and induce oppositely-directed chain kinks. The model predicts equilibrium binding curves for myosin-S1 and TnI as a function of their first-order affinities K(S1) and L(TI). Myosin is detached by the actin binding of TnI, but TnI is more efficiently detached by myosin when the kink size (typically nine to ten actin sites) spans the seven-site spacing between adjacent TnI molecules. An allosteric mechanism is used for coupling the detachment of TnI to calcium binding by TnC. With thermally activated TnI kinks (kink energy B approximately k(B)T), TnI also binds cooperatively to actin, producing cooperative detachment of myosin and biphasic myosin-calcium Hill plots, with Hill coefficients of 2 at high calcium and 4-6 at low calcium as observed in striated muscle. The theory also predicts the cooperative effects observed in the calcium loading of TnC.
Smith
D A
DA
Randall Centre, King's College London, Guy's Campus, London SE1 1UL, UK.
Geeves
M A
MA
D000199:Actins / Q000737:chemistry* / Q000502:physiology; D001665:Binding Sites; D002118:Calcium / Q000737:chemistry* / Q000502:physiology; D003198:Computer Simulation; D005246:Feedback; D006706:Homeostasis; D046911:Macromolecular Substances; D008954:Models, Biological; D008956:Models, Chemical; D008958:Models, Molecular; D020409:Molecular Motor Proteins / Q000737:chemistry* / Q000502:physiology; D009038:Motion; D009119:Muscle Contraction / Q000502:physiology; D009218:Myosins / Q000737:chemistry* / Q000502:physiology; D011485:Protein Binding; D011487:Protein Conformation; D014335:Tropomyosin / Q000737:chemistry* / Q000502:physiology; D014336:Troponin / Q000737:chemistry* / Q000502:physiology
D000199:Actins; D046911:Macromolecular Substances; D020409:Molecular Motor Proteins; D014335:Tropomyosin; D014336:Troponin; D009218:Myosins; D002118:Calcium