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@ARTICLE{Pinotsis:454500,
author = {Pinotsis, Nikos and Zielinska, Karolina and Babuta, Mrigya
and Arolas, Joan L. and Kostan, Julius and Khan, Muhammad
Bashir and Schreiner, Claudia and Salmazo, Anita and
Ciccarelli, Luciano and Puchinger, Martin and Gkougkoulia,
Eirini A. and Ribeiro, Euripedes de Almeida and Marlovits,
Thomas and Bhattacharya, Alok and Djinovic-Carugo, Kristina},
title = {{C}alcium modulates the domain flexibility and function of
an $\alpha$-actinin similar to the ancestral α-actinin},
journal = {Proceedings of the National Academy of Sciences of the
United States of America},
volume = {117},
number = {36},
issn = {1091-6490},
address = {Washington, DC},
publisher = {National Acad. of Sciences},
reportid = {PUBDB-2021-00574},
pages = {22101 - 22112},
year = {2020},
note = {Waiting for fulltext},
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.},
cin = {CSSB-UKE / CSSB-GS / CSSB-UKE-TM},
ddc = {500},
cid = {I:(DE-H253)CSSB-UKE-20141216 / I:(DE-H253)CSSB-GS-20140311
/ I:(DE-H253)CSSB-UKE-TM-20210520},
pnm = {6215 - Soft Matter, Health and Life Sciences (POF3-621)},
pid = {G:(DE-HGF)POF3-6215},
experiment = {EXP:(DE-MLZ)NOSPEC-20140101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32848067},
UT = {WOS:000572964500012},
doi = {10.1073/pnas.1917269117},
url = {https://bib-pubdb1.desy.de/record/454500},
}