TY  - JOUR
AU  - Pinotsis, Nikos
AU  - Zielinska, Karolina
AU  - Babuta, Mrigya
AU  - Arolas, Joan L.
AU  - Kostan, Julius
AU  - Khan, Muhammad Bashir
AU  - Schreiner, Claudia
AU  - Salmazo, Anita
AU  - Ciccarelli, Luciano
AU  - Puchinger, Martin
AU  - Gkougkoulia, Eirini A.
AU  - Ribeiro, Euripedes de Almeida
AU  - Marlovits, Thomas
AU  - Bhattacharya, Alok
AU  - Djinovic-Carugo, Kristina
TI  - Calcium modulates the domain flexibility and function of an α-actinin similar to the ancestral α-actinin
JO  - Proceedings of the National Academy of Sciences of the United States of America
VL  - 117
IS  - 36
SN  - 1091-6490
CY  - Washington, DC
PB  - National Acad. of Sciences
M1  - PUBDB-2021-00574
SP  - 22101 - 22112
PY  - 2020
N1  - Waiting for fulltext
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:32848067
UR  - <Go to ISI:>//WOS:000572964500012
DO  - DOI:10.1073/pnas.1917269117
UR  - https://bib-pubdb1.desy.de/record/454500
ER  -