Tropomyosin diffusion over actin subunits facilitates thin filament assembly.

Stefan Fischer,Jeffrey R Moore,William Lehman,Michael J Rynkiewicz

doi:10.1063/1.4940223

Abstract

Coiled-coil tropomyosin binds to consecutive actin-subunits along actin-containing thin filaments. Tropomyosin molecules then polymerize head-to-tail to form cables that wrap helically around the filaments. Little is known about the assembly process that leads to continuous, gap-free tropomyosin cable formation. We propose that tropomyosin molecules diffuse over the actin-filament surface to connect head-to-tail to partners. This possibility is likely because (1) tropomyosin hovers loosely over the actin-filament, thus binding weakly to F-actin and (2) low energy-barriers provide tropomyosin freedom for 1D axial translation on F-actin. We consider that these unique features of the actin-tropomyosin interaction are the basis of tropomyosin cable formation.

Highlights

Little is known about the assembly process that leads to continuous, gap-free tropomyosin cable formation
True to the maxim that one’s first thoughts can be one’s worst thoughts, the binding properties of single tropomyosin molecules to actin filaments seem incompatible with thin filament assembly and function
Individual tropomyosin molecules bind to actin with extremely low affinity (Ka $ 2 Â 103 MÀ1) (Wegner, 1980), equating to a few times kT; how does tropomyosin bind to and regulate F-actin at all? in what may seem to be improbable, equilibrium binding experiments show that F-actin, once saturated with tropomyosin, interacts with the protein about 1000 times more strongly, and tropomyosin does remain bound to the assembled thin filament

Summary

Introduction

Tropomyosin molecules polymerize head-to-tail to form cables that wrap helically around the filaments. Tropomyosin, the first actin-binding protein to be identified (Bailey, 1946), was proposed by Crick (1953) to form a two-chained a-helical coiled-coiled, a structure characterized further by Szent-Gy€orgyi and Cohen (1957) and Holmes and Cohen (1963).

Results

Conclusion