Mechanical unfolding reveals stable 3-helix intermediates in talin and α-catenin

摘要

Author summary In order to migrate and survive, most cells need to be attached to their environment. Cells anchor to the extracellular matrix via transmembrane integrin, connecting it to contractile the cytoskeleton. Similarly, cell-cell contacts are formed via transmembrane cadherin, which also connects to the contractile cytoskeleton through scaffolding proteins. Examples of such proteins include talin and α-catenin, which connect integrin and cadherin respectively, to actin filaments of the cytoskeleton. Mechanical forces that are transmitted between the cell and its environment activate binding and regulate the functions of these scaffolding proteins at cell-extracellular matrix and cell-cell contacts. Functions of talin and α-catenin are tightly modulated by mechanical forces. The stretching of these proteins under mechanical load exposes buried binding sites for other partners, such as vinculin. We used steered molecular dynamics simulations and single-molecule atomic force microscopy to study how these proteins unfold under load. Our results suggest that α-helical talin and α-catenin unfold through stable 3-helix intermediates. These intermediates represent biologically active states, which may allow recruitment of other binding partners.