Structural insights into calcium-induced conformational changes in human gelsolin

Gelsolin is known as one of the actin-binding proteins capable of severing and capping filamentous actin, and of undergoing structural changes in the presence of calcium ions to interact with actin filaments. In this study, single-particle 3D reconstruction using electron microscopy (EM) revealed that, in the presence of calcium, the structure of gelsolin undergoes structural changes before interacting with actin. These differences are subtle with similarities, as confirmed by the EM map. According to the results of the molecular dynamics simulations, these nuanced structural differences primarily manifest at the domain level when calcium is present. These results provide structural evidence that, in the presence of calcium, gelsolin enters a phase of conformational preparation to transition into the active state. This process enables gelsolin to bind to actin, whereupon gelsolin undergoes more drastic structural changes upon interaction with actin filaments, which allows it to participate in binding and severing to regulate the cytoskeleton. This is the first visualization of full-length gelsolin, and helps to clarify crucial aspects of the as of yet incompletely understood interaction between gelsolin and actin.