6SL2

ALPHA-ACTININ FROM ENTAMOEBA HISTOLYTICA

Summary for 6SL2

• Entry DOI: 10.2210/pdb6sl2/pdb
• Related: 5NL6 5NL7
• Descriptor: Calponin homology domain protein putative, CALCIUM ION, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: actinin, actin binding domain, spectrin repear, calmodulin-like domain, calcium regulation, structural protein
• Biological source: Entamoeba histolytica
• Total number of polymer chains: 1
• Total formula weight: 70198.34

Authors

Pinotsis, N.,Khan, M.B.,Djinovic-Carugo, K. (deposition date: 2019-08-18, release date: 2020-08-26, Last modification date: 2025-04-09)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3.1 Å)