Structure of Ca2+-binding protein-6 from Entamoeba histolytica and its involvement in trophozoite proliferation regulation

PLoS Pathogens
Deepshikha VermaKandala V R Chary

Abstract

Cell cycle of Entamoeba histolytica, the etiological agent of amoebiasis, follows a novel pathway, which includes nuclear division without the nuclear membrane disassembly. We report a nuclear localized Ca2+-binding protein from E. histolytica (abbreviated hereafter as EhCaBP6), which is associated with microtubules. We determined the 3D solution NMR structure of EhCaBP6, and identified one unusual, one canonical and two non-canonical cryptic EF-hand motifs. The cryptic EF-II and EF-IV pair with the Ca2+-binding EF-I and EF-III, respectively, to form a two-domain structure similar to Calmodulin and Centrin proteins. Downregulation of EhCaBP6 affects cell proliferation by causing delays in transition from G1 to S phase, and inhibition of DNA synthesis and cytokinesis. We also demonstrate that EhCaBP6 modulates microtubule dynamics by increasing the rate of tubulin polymerization. Our results, including structural inferences, suggest that EhCaBP6 is an unusual CaBP involved in regulating cell proliferation in E. histolytica similar to nuclear Calmodulin.

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Citations

Mar 23, 2018·Parasitology·Marina A Gwairgi, Reena Ghildyal
May 8, 2020·PLoS Pathogens·Mrigya BabutaAlok Bhattacharya
Dec 12, 2019·Frontiers in Cellular and Infection Microbiology·Tansy C Hammarton
Aug 22, 2020·International Journal for Parasitology·Magda Reyes-LópezMireya de la Garza

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Methods Mentioned

BETA
NMR
gel-filtration
dynamic light scattering
circular dichroism
isothermal titration calorimetry
pull down
Surface Plasmon Resonance
light scattering
FACS
transfection

Software Mentioned

TATAPRO
Elements Analysis
CARA
Cell quest
PROCHECK
GraphPad Prism
TopSpin
AlphaEaseFc
MODFIT
VMD

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