Using Fluorescent Myosin to Directly Visualize Cooperative Activation of Thin Filaments

Desai, R. A. and Geeves, M. A. and Kad, Neil M (2015) Using Fluorescent Myosin to Directly Visualize Cooperative Activation of Thin Filaments. Journal of Biological Chemistry, . jbc.M114.609743-jbc.M114.609743. ISSN 0021-9258. (doi:https://doi.org/10.1074/jbc.M114.609743) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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Official URL
http://dx.doi.org/10.1074/jbc.M114.609743

Abstract

Contraction of striated muscle is tightly regulated by the release and sequestration of calcium within myocytes. At the molecular level, calcium modulates myosin’s access to the thin filament. Once bound, myosin is hypothesized to potentiate the binding of further myosins. Here we directly image single molecules of myosin binding to and activating thin filaments. Using this approach the cooperative binding of myosin along thin filaments has been quantified. We have found that two myosin heads are required to laterally activate a regulatory unit of thin filament. The regulatory unit is found to be capable of accommodating 11 further myosins. Three thin filament activation states possessing differential myosin binding capacities are also visible. To describe this system we have formulated a simple chemical kinetic model of cooperative activation that holds across a wide range of solution conditions. The stochastic nature of activation is strongly highlighted by data obtained in sub-optimal activation conditions where the generation of activation waves and their catastrophic collapse can be observed. This suggests that the thin filament has the potential to be turned fully on or off on a binary fashion.

Item Type: Article
Uncontrolled keywords: single-molecule biophysics, muscle regulation, cooperativity, tropomyosin, troponin, actin
Subjects: Q Science
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: N. Kad
Date Deposited: 10 Dec 2014 10:07 UTC
Last Modified: 10 Dec 2017 11:33 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/45930 (The current URI for this page, for reference purposes)
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