Cooperative regulation of myosin-actin interactions by a continuous flexible chain I: actin-tropomyosin systems.
We present a model for cooperative myosin binding to the regulated actin filament, where tropomyosins are treated as a weakly-confined continuous flexible chain covering myosin binding sites. Thermal fluctuations in chain orientation are initially required for myosin binding, leaving kinked regions under which subsequent myosins may bind without further distortion of the chain. Statistical mechanics predicts the fraction of sites with bound myosin-S1 as a function of their affinities. Published S1 binding curves to regulated filaments with different tropomyosin isoforms are fitted by varying the binding constant, chain persistence length nu (in actin monomers), and chain kink energy A from a single bound S1. With skeletal tropomyosin, we find an S1 actin-binding constant of 2.2 x 10(7) M(-1), A = 1.6 k(B)T and nu = 2.7. Similar persistence lengths are found with yeast tropomyosin. Larger values are found for tropomyosin-troponin in the presence of calcium (nu = 3.7) and tropomyosins from smooth muscle and fibroblasts (nu = 4.5). The relationship of these results to structural information and the rigid-unit model of McKillop and Geeves is discussed.
Smith
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Randall Centre, King's College London, Guy's Campus, London SE1 1UL, UK. david.smith@med.monash.edu.au
Maytum
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Geeves
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D000199:Actins / Q000737:chemistry* / Q000502:physiology*; D001665:Binding Sites; 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*
D000199:Actins; D046911:Macromolecular Substances; D020409:Molecular Motor Proteins; D014335:Tropomyosin; D009218:Myosins