期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2020
卷号：117
期号：36
页码：22101-22112
DOI：10.1073/pnas.1917269117
出版社：The National Academy of Sciences of the United States of America
摘要：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 2 in nonmuscle cells. Here we report the mechanism of Ca 2 -mediated regulation of Entamoeba histolytica α-actinin-2 ( Eh Actn2) with features expected for the common ancestor of Entamoeba and higher eukaryotic α-actinins. Crystal structures of Ca 2 -free and Ca 2 -bound Eh Actn2 reveal a calmodulin-like domain (CaMD) uniquely inserted within the rod domain. Integrative studies reveal an exceptionally high affinity of the Eh Actn2 CaMD for Ca 2 , binding of which can only be regulated in the presence of physiological concentrations of Mg 2 . Ca 2 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 Eh Actn2 plays an important role in phagocytic cup formation and might constitute a new drug target for amoebic dysentery.
关键词：α-actinin ; F-actin bundling and binding ; calcium regulation ; modulation of structural rigidity ; crystal structure
