Calcium modulates the domain flexibility and function of an α-actinin similar to the ancestral α-actinin
Nikos Pinotsis, Karolina Zielinska, Mrigya Babuta, Joan L. Arolas, Július Košťan, Muhammad Bashir Khan, Claudia Schreiner, Anita Salmazo, Luciano Ciccarelli, Martin Puchinger, Eirini A. Gkougkoulia, Euripedes de Almeida Ribeiro, Thomas C. Marlovits, Alok Bhattacharya, Kristina Djinović‐Carugo
Abstract
Significance Actin is one of the most abundant proteins in eukaryotic cells. Actin filaments together with a large number of actin-binding proteins are critical players in many cellular functions, ranging from cell motility and muscle contraction to maintenance of cell shape and transcription regulation. α-Actinin—a member of the spectrin superfamily—is an archetypical F-actin–binding and –bundling protein. It is known that Ca 2+ inhibits α-actinin capacity to bundle F-actin. We present a structure of a Ca 2+ -regulated α-actinin and propose the mechanism for its regulation. We uncover that Ca 2+ binding triggers an increase in protein rigidity, leading to reduced conformational flexibility and bundling activity. The proposed molecular mechanism is likely to be a blueprint for regulation of spectrin-like proteins.