5NL7

The crystal structure of the Actin Binding Domain (ABD) of alpha actinin from Entamoeba histolytica

5NL7 の概要

• エントリーDOI: 10.2210/pdb5nl7/pdb
• 分子名称: Calponin homology domain protein putative, CALCIUM ION, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ... (4 entities in total)
• 機能のキーワード: actin binding domain, actinin, entamoeba histolytica, structural protein
• 由来する生物種: Entamoeba histolytica
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 53027.56

構造登録者

Pinotsis, N.,Djinovic-Carugo, K.,Khan, M.B. (登録日: 2017-04-04, 公開日: 2018-05-16, 最終更新日: 2024-11-06)

主引用文献

Pinotsis, N.,Zielinska, K.,Babuta, M.,Arolas, J.L.,Kostan, J.,Khan, M.B.,Schreiner, C.,Salmazo, A.,Ciccarelli, L.,Puchinger, M.,Gkougkoulia, E.A.,Ribeiro Jr., E.A.,Marlovits, T.C.,Bhattacharya, A.,Djinovic-Carugo, K.
Calcium modulates the domain flexibility and function of an alpha-actinin similar to the ancestral alpha-actinin.
Proc.Natl.Acad.Sci.USA, 117:22101-22112, 2020

PubMed Abstract: 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 in nonmuscle cells. Here we report the mechanism of Ca-mediated regulation of α-actinin-2 (Actn2) with features expected for the common ancestor of and higher eukaryotic α-actinins. Crystal structures of Ca-free and Ca-bound Actn2 reveal a calmodulin-like domain (CaMD) uniquely inserted within the rod domain. Integrative studies reveal an exceptionally high affinity of the Actn2 CaMD for Ca, binding of which can only be regulated in the presence of physiological concentrations of Mg Ca 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 Actn2 plays an important role in phagocytic cup formation and might constitute a new drug target for amoebic dysentery.

PubMed: 32848067
DOI: 10.1073/pnas.1917269117

実験手法

X-RAY DIFFRACTION (2.48 Å)