Tropomyosin dynamics

Abstract

Tropomyosin is a two chained α-helical coiled coil protein that binds actin filaments and interacts with various actin binding proteins. Tropomyosin function depends on its ability to move to distinct locations on the surface of actin in response to the binding of different thin filament effectors. Tropomyosin dynamics plays an important role in these fluctuating interactions with actin and is thought to be fundamental to many of its biological activities. For example tropomyosin concerted movement on the surface of actin triggered by Ca(2+) binding to troponin or myosin head binding to actin has been argued to be key to the cooperative allosteric regulation of muscle contraction. These large-scale motions are affected by tropomyosin internal dynamics and mechanical properties. Tropomyosin internal dynamics corresponding to smaller and more localised structural fluctuations are increasingly recognised to play an important role in its function. A thorough understanding of the coupling between local and global structural fluctuations in tropomyosin is required to understand how time dependent structural fluctuations in tropomyosin contribute to the overall thin filament dynamics and dictate their various biological activities.

Tropomyosin isoforms differentially affect muscle contractility in the head and body regions of the nematodeCaenorhabditis elegans

“…Although we did not detect a difference between LEV-11O and LEV-11A in the affinity with actin in vitro, there may be a significant difference in muscle thin filament regulation in the presence of troponin in vivo. In thin filaments, tropomyosin binds to actin only weakly, with a distance of ∼10 Å from the surface of actin to allow rapid troponin-regulated movement ( Holmes and Lehman, 2008 ; El-Mezgueldi, 2014 ; Rynkiewicz et al , 2017 ). Therefore, the difference between a heptad of LEV-11O and LEV-11A may affect their dynamic biophysical properties, which may be of functional significance.…”

Thin Filament Structure and the Steric Blocking Model

“…Tropomyosin is often described as fundamental to the cooperative allosteric regulation of muscle contraction (47,129,130,133,145). The term allosteric when conjoined with descriptions of steric effects can be confusing.…”

Building Blocks of Functioning Brain: Cytoskeletal Dynamics in Neuronal Development

“…They are derived from four genes, and via alternative splicing there are >40 isoforms (El-Mezgueldi, 2014; Marston and Gautel, 2013), a specific subset of which are expressed in neurons (Schevzov et al, 1997). Early studies indicate that Tm4, Tm5a, and Tm5b isoforms are enriched in growth cones of developing neurons, whereas Tm5NM1 (tropomyosin 3, gamma) localizes to the axon hillock and proximal regions of axons and dendrites, and TmBr3 to presynaptic terminals (Had et al, 1994; Schevzov et al, 1997; Weinberger et al, 1996).…”