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ATP2, The essential P4-ATPase of malaria parasites, catalyzes lipid-stimulated ATP hydrolysis in complex with a Cdc50 β-subunit
Lamy, Anaïs (Umeå University)
Macarini-Bruzaferro, Ewerton (University of São Paulo)
Dieudonné, Thibaud (Aarhus University)
Peralvarez-Marin, Alex (Universitat Autònoma de Barcelona. Facultat de Medicina)
Lenoir, Guillaume (Université Paris-Saclay, CEA, CNRS)
Montigny, Cédric (Université Paris-Saclay, CEA, CNRS)
le Maire, Marc (Université Paris-Saclay, CEA, CNRS)
Vázquez-Ibar, José Luis (Université Paris-Saclay, CEA, CNRS)

Data: 2021
Resum: Gene targeting approaches have demonstrated the essential role for the malaria parasite of membrane transport proteins involved in lipid transport and in the maintenance of membrane lipid asymmetry, representing emerging oportunites for therapeutical intervention. This is the case of ATP2, a Plasmodium -encoded 4 P-type ATPase (P4-ATPase or lipid flippase), whose activity is completely irreplaceable during the asexual stages of the parasite. Moreover, a recent chemogenomic study has situated ATP2 as the possible target of two antimalarial drug candidates. In eukaryotes, P4-ATPases assure the asymmetric phospholipid distribution in membranes by translocating phospholipids from the outer to the inner leaflet. In this work, we have used a recombinantly-produced P. chabaudi ATP2 (PcATP2), to gain insights into the function and structural organization of this essential transporter. Our work demonstrates that PcATP2 associates with two of the three Plasmodium- encoded Cdc50 proteins: PcCdc50B and PcCdc50A. Purified PcATP2/PcCdc50B complex displays ATPase activity in the presence of either phosphatidylserine or phosphatidylethanolamine. In addition, this activity is upregulated by phosphatidylinositol 4-phosphate. Overall, our work describes the first biochemical characterization of a Plasmodium lipid flippase, a first step towards the understanding of the essential physiological role of this transporter and towards its validation as a potential antimalarial drug target.
Drets: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Llengua: Anglès
Document: Article ; recerca ; Versió publicada
Matèria: Malaria ; P4-ATPases ; Lipid flippase ; PfATP2 ; Membrane transport proteins ; Heterologous expression
Publicat a: Emerging microbes & infections, Vol. 10 (january 2021) , p. 132-147, ISSN 2222-1751

DOI: 10.1080/22221751.2020.1870413
PMID: 33372863


16 p, 2.0 MB

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 Registre creat el 2021-04-12, darrera modificació el 2023-01-15



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