Phosphorylation of Ser283 enhances the stiffness of the tropomyosin head-to-tail overlap domain.

Lehman, William and Medlock, Greg and Li, Xiaochuan (Edward) and Suphamungmee, Worawit and Tu, An-Yue and Schmidtmann, Anja and Ujfalusi, Zoltán and Fischer, Stefan and Moore, Jeffrey R. and Geeves, Michael A. and Regnier, Michael (2015) Phosphorylation of Ser283 enhances the stiffness of the tropomyosin head-to-tail overlap domain. Archives of Biochemistry and Biophysics, 571 . pp. 10-15. ISSN 0003-9861. (doi:https://doi.org/10.1016/j.abb.2015.02.026) (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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http://doi.org/10.1016/j.abb.2015.02.026

Abstract

The ends of coiled-coil tropomyosin molecules are joined together by nine to ten residue-long head-to-tail “overlapping domains”. These short four-chained interconnections ensure formation of continuous tropomyosin cables that wrap around actin filaments. Molecular Dynamics simulations indicate that the curvature and bending flexibility at the overlap is 10–20% greater than over the rest of the molecule, which might affect head-to-tail filament assembly on F-actin. Since the penultimate residue of striated muscle tropomyosin, Ser283, is a natural target of phosphorylating enzymes, we have assessed here if phosphorylation adjusts the mechanical properties of the tropomyosin overlap domain. MD simulations show that phosphorylation straightens the overlap to match the curvature of the remainder of tropomyosin while stiffening it to equal or exceed the rigidity of canonical coiled-coil regions. Corresponding EM data on phosphomimetic tropomyosin S283D corroborate these findings. The phosphorylation-induced change in mechanical properties of tropomyosin likely results from electrostatic interactions between C-terminal phosphoSer283 and N-terminal Lys12 in the four-chain overlap bundle, while promoting stronger interactions among surrounding residues and thus facilitating tropomyosin cable assembly. The stiffening effect of D283-tropomyosin noted correlates with previously observed enhanced actin–tropomyosin activation of myosin S1-ATPase, suggesting a role for the tropomyosin phosphorylation in potentiating muscle contraction.

Item Type: Article
Subjects: Q Science
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Sue Davies
Date Deposited: 12 Oct 2015 15:02 UTC
Last Modified: 13 Oct 2015 07:54 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/50886 (The current URI for this page, for reference purposes)
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