EhCoactosin Stabilizes Actin Filaments in the Protist Parasite


E. histolytica is an important pathogen and a major cause of morbidity and mortality in developing nations. High level of motility and phagocytosis is responsible for the parasite invading different tissues of the host. Phagocytosis and motility depend on highly dynamic actin cytoskeleton of this organism. The mechanisms of actin dynamics is not well understood in E. histolytica. Here we report that coactosin like molecule from E. histolytica, EhCoactosin is involved in F-actin stabilization. The crystal structure obtained for the protein provides explanation for some functional differences observed with respect to the human homologue, such as ability to bind G-actin. Moreover, computational modelling along with crystal structure helps to explain the F-actin binding and stabilization by wild type protein. The mutational analysis further suggests that F-actin binding property does not depend on conserved Lys75 residue as observed in Human coactosin like protein (HCLP) but other regions present in protein are involved in binding. Overexpression of this protein in trophozoites leads to stabilization of actin filaments which are not accessible to actin remodelling machinery thereby reducing the growth of parasite due to decreased rate of actin dependent endocytosis. Overall, EhCoactosin behaves as F-actin stabilizing protein in vitro and it also participates in processes like phagocytosis and pseudopod formation.


Vyšlo v časopise: EhCoactosin Stabilizes Actin Filaments in the Protist Parasite. PLoS Pathog 10(9): e32767. doi:10.1371/journal.ppat.1004362
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.ppat.1004362

Souhrn

E. histolytica is an important pathogen and a major cause of morbidity and mortality in developing nations. High level of motility and phagocytosis is responsible for the parasite invading different tissues of the host. Phagocytosis and motility depend on highly dynamic actin cytoskeleton of this organism. The mechanisms of actin dynamics is not well understood in E. histolytica. Here we report that coactosin like molecule from E. histolytica, EhCoactosin is involved in F-actin stabilization. The crystal structure obtained for the protein provides explanation for some functional differences observed with respect to the human homologue, such as ability to bind G-actin. Moreover, computational modelling along with crystal structure helps to explain the F-actin binding and stabilization by wild type protein. The mutational analysis further suggests that F-actin binding property does not depend on conserved Lys75 residue as observed in Human coactosin like protein (HCLP) but other regions present in protein are involved in binding. Overexpression of this protein in trophozoites leads to stabilization of actin filaments which are not accessible to actin remodelling machinery thereby reducing the growth of parasite due to decreased rate of actin dependent endocytosis. Overall, EhCoactosin behaves as F-actin stabilizing protein in vitro and it also participates in processes like phagocytosis and pseudopod formation.


Zdroje

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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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PLOS Pathogens


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