Cooperativity and Frustration in Protein-Mediated Parallel Actin Bundles

TL;DR

This study investigates how fascin and espin proteins mediate actin filament bundling, revealing that linker flexibility and geometry influence cooperative binding and the resulting filament twist states.

Contribution

It introduces a coarse-grained model explaining how linker stiffness and geometry determine bundling mechanisms and filament twist in actin-protein interactions.

Findings

Fascin induces a spectrum of intermediate twist states in actin bundles.

Espin results in untwisted or fully-overtwisted actin bundles.

Linker flexibility and geometry are key to cooperative binding mechanisms.

Abstract

We examine the mechanism of bundling of cytoskeletal actin filaments by two representative bundling proteins, fascin and espin. Small-angle X-ray studies show that increased binding from linkers drives a systematic \textit{overtwist} of actin filaments from their native state, which occurs in a linker-dependent fashion. Fascin bundles actin into a continuous spectrum of intermediate twist states, while espin only allows for untwisted actin filaments and fully-overtwisted bundles. Based on a coarse-grained, statistical model of protein binding, we show that the interplay between binding geometry and the intrinsic \textit{flexibility} of linkers mediates cooperative binding in the bundle. We attribute the respective continuous/discontinous bundling mechanisms of fascin/espin to differences in the stiffness of linker bonds themselves.