مورد إلكتروني
ATP2, The essential P4-ATPase of malaria parasites, catalyzes lipid-stimulated ATP hydrolysis in complex with a Cdc50 β-subunit
| العنوان: | ATP2, The essential P4-ATPase of malaria parasites, catalyzes lipid-stimulated ATP hydrolysis in complex with a Cdc50 β-subunit |
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| بيانات النشر: | Umeå universitet, Institutionen för medicinsk kemi och biofysik Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Gif-sur-Yvette, France 2021 |
| تفاصيل مُضافة: | Lamy, Anaïs Macarini-Bruzaferro, Ewerton Dieudonné, Thibaud Perálvarez-Marin, Alex Lenoir, Guillaume Montigny, Cédric le Maire, Marc Vazquez-Ibar, José Luis |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | 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. |
| مصطلحات الفهرس: | Malaria, P4-ATPases, lipid flippase, PfATP2, membrane transport proteins, heterologous expression, Biochemistry and Molecular Biology, Biokemi och molekylärbiologi, Article in journal, info:eu-repo/semantics/article, text |
| DOI: | 10.1080.22221751.2020.1870413 |
| URL: | Emerging Microbes & Infections, 2021, 10:1, s. 132-147 |
| الإتاحة: | Open access content. Open access content info:eu-repo/semantics/openAccess |
| ملاحظة: | application/pdf English |
| أرقام أخرى: | UPE oai:DiVA.org:umu-180219 doi:10.1080/22221751.2020.1870413 PMID 33372863 ISI:000610539800001 Scopus 2-s2.0-85099716441 1247749575 |
| المصدر المساهم: | UPPSALA UNIV LIBR From OAIster®, provided by the OCLC Cooperative. |
| رقم الأكسشن: | edsoai.on1247749575 |
| قاعدة البيانات: | OAIster |
| DOI: | 10.1080.22221751.2020.1870413 |
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