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

PLoS Pathogens

Deepshikha Verma¹  Alok Bhattacharya²  Kandala V. R. Chary²  Samudrala Gourinath²  Aruna Murmu³ 

[1] Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai, India;School of Life Sciences, Jawaharlal Nehru University, New Delhi, India;Tata Institute of Fundamental Research, Center for Interdisciplinary Sciences, Hyderabad, India

关键词: Cell cycle;    cell division;    Entamoeba histolytica;    Microtubules;    Immunostaining;    Tubulins;    Parasitic cell cycles;    Tetracyclines;    DNA synthesis;   

DOI  :  10.1371/journal.ppat.1006332

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY