%0 Journal Article
%A Pinotsis, Nikos
%A Zielinska, Karolina
%A Babuta, Mrigya
%A Arolas, Joan L.
%A Kostan, Julius
%A Khan, Muhammad Bashir
%A Schreiner, Claudia
%A Salmazo, Anita
%A Ciccarelli, Luciano
%A Puchinger, Martin
%A Gkougkoulia, Eirini A.
%A Ribeiro, Euripedes de Almeida
%A Marlovits, Thomas
%A Bhattacharya, Alok
%A Djinovic-Carugo, Kristina
%T Calcium modulates the domain flexibility and function of an α-actinin similar to the ancestral α-actinin
%J Proceedings of the National Academy of Sciences of the United States of America
%V 117
%N 36
%@ 1091-6490
%C Washington, DC
%I National Acad. of Sciences
%M PUBDB-2021-00574
%P 22101 - 22112
%D 2020
%Z Waiting for fulltext
%X The actin cytoskeleton, a dynamic network of actin filaments and associated F-actin–binding proteins, is fundamentally important in eukaryotes. α-Actinins are major F-actin bundlers that are inhibited by Ca<sup>2+</sup> in nonmuscle cells. Here we report the mechanism of Ca<sup>2+</sup>-mediated regulation of Entamoeba histolytica α-actinin-2 (EhActn2) with features expected for the common ancestor of Entamoeba and higher eukaryotic α-actinins. Crystal structures of Ca<sup>2+</sup>-free and Ca<sup>2+</sup>-bound EhActn2 reveal a calmodulin-like domain (CaMD) uniquely inserted within the rod domain. Integrative studies reveal an exceptionally high affinity of the EhActn2 CaMD for Ca<sup>2+</sup>, binding of which can only be regulated in the presence of physiological concentrations of Mg<sup>2+</sup>. C<sup>2+</sup> binding triggers an increase in protein multidomain rigidity, reducing conformational flexibility of F-actin–binding domains via interdomain cross-talk and consequently inhibiting F-actin bundling. In vivo studies uncover that EhActn2 plays an important role in phagocytic cup formation and might constitute a new drug target for amoebic dysentery.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:32848067
%U <Go to ISI:>//WOS:000572964500012
%R 10.1073/pnas.1917269117
%U https://bib-pubdb1.desy.de/record/454500