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• W2181917945 startingPage "e1004599" @default.
• W2181917945 abstract "Muscle contracts due to ATP-dependent interactions of myosin motors with thin filaments composed of the proteins actin, troponin, and tropomyosin. Contraction is initiated when calcium binds to troponin, which changes conformation and displaces tropomyosin, a filamentous protein that wraps around the actin filament, thereby exposing myosin binding sites on actin. Myosin motors interact with each other indirectly via tropomyosin, since myosin binding to actin locally displaces tropomyosin and thereby facilitates binding of nearby myosin. Defining and modeling this local coupling between myosin motors is an open problem in muscle modeling and, more broadly, a requirement to understanding the connection between muscle contraction at the molecular and macro scale. It is challenging to directly observe this coupling, and such measurements have only recently been made. Analysis of these data suggests that two myosin heads are required to activate the thin filament. This result contrasts with a theoretical model, which reproduces several indirect measurements of coupling between myosin, that assumes a single myosin head can activate the thin filament. To understand this apparent discrepancy, we incorporated the model into stochastic simulations of the experiments, which generated simulated data that were then analyzed identically to the experimental measurements. By varying a single parameter, good agreement between simulation and experiment was established. The conclusion that two myosin molecules are required to activate the thin filament arises from an assumption, made during data analysis, that the intensity of the fluorescent tags attached to myosin varies depending on experimental condition. We provide an alternative explanation that reconciles theory and experiment without assuming that the intensity of the fluorescent tags varies." @default.
• W2181917945 created "2016-06-24" @default.
• W2181917945 creator A5075473900 @default.
• W2181917945 creator A5090820903 @default.
• W2181917945 date "2015-11-04" @default.
• W2181917945 modified "2023-10-02" @default.
• W2181917945 title "Direct Measurements of Local Coupling between Myosin Molecules Are Consistent with a Model of Muscle Activation" @default.
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• W2181917945 doi "https://doi.org/10.1371/journal.pcbi.1004599" @default.
• W2181917945 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4633106" @default.
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• W2181917945 hasPublicationYear "2015" @default.
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