Journal Article

PUBDB-2021-00574

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Calcium modulates the domain flexibility and function of an $\alpha$-actinin similar to the ancestral α-actinin

Pinotsis, N. ; Zielinska, K. ; Babuta, M. ; Arolas, J. L. ; Kostan, J. ; Khan, M. B. ; Schreiner, C. ; Salmazo, A. ; Ciccarelli, L.DESY* ; Puchinger, M. ; Gkougkoulia, E. A. ; Ribeiro, E. d. A. ; Marlovits, T.CSSB*DESY* ; Bhattacharya, A. ; Djinovic-Carugo, K. (Corresponding author)

2020
National Acad. of Sciences Washington, DC

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Please use a persistent id in citations: doi:10.1073/pnas.1917269117

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$^{2+}$ in nonmuscle cells. Here we report the mechanism of Ca$^{2+}$-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$^{2+}$-free and Ca$^{2+}$-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$^{2+}$, binding of which can only be regulated in the presence of physiological concentrations of Mg$^{2+}$. C$^{2+}$ 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 EhActn2 plays an important role in phagocytic cup formation and might constitute a new drug target for amoebic dysentery.

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Contributing Institute(s):

1. CSSB-UKE (CSSB-UKE)
2. Centre for Structural Systems Biology (CSSB-GS)
3. CSSB-UKE-TM (CSSB-UKE-TM)

Research Program(s):

1. 6215 - Soft Matter, Health and Life Sciences (POF3-621) (POF3-621)

Experiment(s):

1. No specific instrument

Appears in the scientific report 2020

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; National-Konsortium ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

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