Calcium modulates the domain flexibility and function of an α-actinin similar to the ancestral α-actinin.

Autor:	Pinotsis N; Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna, A-1030 Vienna, Austria., Zielinska K; Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna, A-1030 Vienna, Austria., Babuta M; School of Life Sciences, Jawaharlal Nehru University, 110067 New Delhi, India., Arolas JL; Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna, A-1030 Vienna, Austria., Kostan J; Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna, A-1030 Vienna, Austria., Khan MB; Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna, A-1030 Vienna, Austria., Schreiner C; Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna, A-1030 Vienna, Austria., Salmazo A; Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna, A-1030 Vienna, Austria., Ciccarelli L; Centre for Structural Systems Biology, D-22607 Hamburg, Germany.; Institute for Structure and Systems Biology, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg, Germany.; Deutsches Elektronen-Synchrotron, D-22607 Hamburg, Germany.; Institute of Molecular Biotechnology, Austrian Academy of Sciences, A-1030 Vienna, Austria.; Research Institute of Molecular Pathology, A-1030 Vienna, Austria., Puchinger M; Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna, A-1030 Vienna, Austria., Gkougkoulia EA; Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna, A-1030 Vienna, Austria., Ribeiro EA Jr; Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna, A-1030 Vienna, Austria., Marlovits TC; Centre for Structural Systems Biology, D-22607 Hamburg, Germany.; Institute for Structure and Systems Biology, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg, Germany.; Deutsches Elektronen-Synchrotron, D-22607 Hamburg, Germany.; Institute of Molecular Biotechnology, Austrian Academy of Sciences, A-1030 Vienna, Austria.; Research Institute of Molecular Pathology, A-1030 Vienna, Austria., Bhattacharya A; School of Life Sciences, Jawaharlal Nehru University, 110067 New Delhi, India., Djinovic-Carugo K; Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna, A-1030 Vienna, Austria; kristina.djinovic@univie.ac.at.; Department of Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, SI-1000 Ljubljana, Slovenia.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2020 Sep 08; Vol. 117 (36), pp. 22101-22112. Date of Electronic Publication: 2020 Aug 26.
DOI:	10.1073/pnas.1917269117
Abstrakt:	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. Competing Interests: The authors declare no competing interest.
Databáze:	MEDLINE
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