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

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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; Macarini-Bruzaferro, Ewerton; Dieudonné, Thibaud et al.

In: Emerging Microbes and Infections, Vol. 10, No. 1, 01.2021, p. 132-147.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Lamy, A, Macarini-Bruzaferro, E, Dieudonné, T, Perálvarez-Marín, A, Lenoir, G, Montigny, C, le Maire, M & Vázquez-Ibar, JL 2021, 'ATP2, The essential P4-ATPase of malaria parasites, catalyzes lipid-stimulated ATP hydrolysis in complex with a Cdc50 β-subunit', Emerging Microbes and Infections, vol. 10, no. 1, pp. 132-147. https://doi.org/10.1080/22221751.2020.1870413

APA

Lamy, A., Macarini-Bruzaferro, E., Dieudonné, T., Perálvarez-Marín, A., Lenoir, G., Montigny, C., le Maire, M., & Vázquez-Ibar, J. L. (2021). ATP2, The essential P4-ATPase of malaria parasites, catalyzes lipid-stimulated ATP hydrolysis in complex with a Cdc50 β-subunit. Emerging Microbes and Infections, 10(1), 132-147. https://doi.org/10.1080/22221751.2020.1870413

CBE

Lamy A, Macarini-Bruzaferro E, Dieudonné T, Perálvarez-Marín A, Lenoir G, Montigny C, le Maire M, Vázquez-Ibar JL. 2021. ATP2, The essential P4-ATPase of malaria parasites, catalyzes lipid-stimulated ATP hydrolysis in complex with a Cdc50 β-subunit. Emerging Microbes and Infections. 10(1):132-147. https://doi.org/10.1080/22221751.2020.1870413

MLA

Vancouver

Lamy A, Macarini-Bruzaferro E, Dieudonné T, Perálvarez-Marín A, Lenoir G, Montigny C et al. ATP2, The essential P4-ATPase of malaria parasites, catalyzes lipid-stimulated ATP hydrolysis in complex with a Cdc50 β-subunit. Emerging Microbes and Infections. 2021 Jan;10(1):132-147. https://doi.org/10.1080/22221751.2020.1870413

Author

Lamy, Anaïs ; Macarini-Bruzaferro, Ewerton ; Dieudonné, Thibaud et al. / ATP2, The essential P4-ATPase of malaria parasites, catalyzes lipid-stimulated ATP hydrolysis in complex with a Cdc50 β-subunit. In: Emerging Microbes and Infections. 2021 ; Vol. 10, No. 1. pp. 132-147.

Bibtex

@article{2d7163c601c94bf39c2f327952b7383f,
title = "ATP2, The essential P4-ATPase of malaria parasites, catalyzes lipid-stimulated ATP hydrolysis in complex with a Cdc50 β-subunit",
abstract = "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.",
keywords = "heterologous expression, lipid flippase, Malaria, membrane transport proteins, P4-ATPases, PfATP2",
author = "Ana{\"i}s Lamy and Ewerton Macarini-Bruzaferro and Thibaud Dieudonn{\'e} and Alex Per{\'a}lvarez-Mar{\'i}n and Guillaume Lenoir and C{\'e}dric Montigny and {le Maire}, Marc and V{\'a}zquez-Ibar, {Jos{\'e} Luis}",
note = "Publisher Copyright: {\textcopyright} 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = jan,
doi = "10.1080/22221751.2020.1870413",
language = "English",
volume = "10",
pages = "132--147",
journal = "Emerging Microbes and Infections",
issn = "2222-1751",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - ATP2, The essential P4-ATPase of malaria parasites, catalyzes lipid-stimulated ATP hydrolysis in complex with a Cdc50 β-subunit

AU - Lamy, Anaïs

AU - Macarini-Bruzaferro, Ewerton

AU - Dieudonné, Thibaud

AU - Perálvarez-Marín, Alex

AU - Lenoir, Guillaume

AU - Montigny, Cédric

AU - le Maire, Marc

AU - Vázquez-Ibar, José Luis

N1 - Publisher Copyright: © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/1

Y1 - 2021/1

N2 - 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.

AB - 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.

KW - heterologous expression

KW - lipid flippase

KW - Malaria

KW - membrane transport proteins

KW - P4-ATPases

KW - PfATP2

UR - http://www.scopus.com/inward/record.url?scp=85099716441&partnerID=8YFLogxK

U2 - 10.1080/22221751.2020.1870413

DO - 10.1080/22221751.2020.1870413

M3 - Journal article

C2 - 33372863

AN - SCOPUS:85099716441

VL - 10

SP - 132

EP - 147

JO - Emerging Microbes and Infections

JF - Emerging Microbes and Infections

SN - 2222-1751

IS - 1

ER -