Chiral twisting in cytoskeletal polymers regulates filament size and orientation

Abstract

<jats:title>Abstract</jats:title><jats:p>While cytoskeletal proteins in the actin family are structurally similar, as filaments they act as critical components of diverse cellular processes across all kingdoms of life. In many rod-shaped bacteria, the actin homolog MreB directs cell-wall insertion and maintains cell shape, but it remains unclear how structural changes to MreB affect its physiological function. To bridge this gap, we performed molecular dynamics simulations for <jats:italic>Caulobacter crescentus</jats:italic> MreB and then utilized a coarse-grained biophysical model to successfully predict MreB filament properties <jats:italic>in vivo.</jats:italic> We discovered that MreB double protofilaments exhibit left-handed twisting that is dependent on the bound nucleotide and membrane binding; the degree of twisting determines the limit length and orientation of MreB filaments <jats:italic>in vivo.</jats:italic> Membrane binding of MreB also induces a stable membrane curvature that is physiologically relevant. Together, our data empower the prediction of cytoskeletal filament size from molecular dynamics simulations, providing a paradigm for connecting protein filament structure and mechanics to cellular functions.</jats:p>