ATP2, The essential P4-ATPase of malaria parasites, catalyzes lipid-stimulated ATP hydrolysis in complex with a Cdc50 beta-subunit

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Arquivos
art_LAMY_ATP2_The_essential_P4ATPase_of_malaria_parasites_catalyzes_2021.PDF (2.4 MB)
Citações na Scopus
10
Tipo de produção
article
Data de publicação
2021
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
TAYLOR & FRANCIS LTD
Autores
LAMY, Anais
DIEUDONNE, Thibaud
PERALVAREZ-MARIN, Alex
LENOIR, Guillaume
MONTIGNY, Cedric
MAIRE, Marc le
VAZQUEZ-IBAR, Jose Luis
Citação
EMERGING MICROBES & INFECTIONS, v.10, n.1, p.132-147, 2021
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
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.
Palavras-chave
Malaria, P4-ATPases, lipid flippase, PfATP2, membrane transport proteins, heterologous expression
URI
https://observatorio.fm.usp.br/handle/OPI/39413
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Coleções
Artigos e Materiais de Revistas Científicas - FM/Outros
Artigos e Materiais de Revistas Científicas - LIM/51
Artigos e Materiais de Revistas Científicas - ODS/03