P-Type ATPase Apt1 of the fungal pathogen Cryptococcus neoformans is a lipid flippase of broad substrate specificity

dc.creatorStanchev, Lyubomir Dimitrov
dc.creatorRizzo, Juliana
dc.creatorPeschel, Rebecca
dc.creatorPazurek, Lilli A.
dc.creatorBredegaard, Lasse
dc.creatorVeit, Sarina
dc.creatorLaerbusch, Sabine
dc.creatorRodrigues, Marcio Lourenço
dc.creatorLópez-Marqués, Rosa L.
dc.creatorPomorski, Thomas Günther
dc.date2021-11-24T12:32:12Z
dc.date2021-11-24T12:32:12Z
dc.date2021
dc.date.accessioned2023-09-26T22:48:45Z
dc.date.available2023-09-26T22:48:45Z
dc.identifierSTANCHEV, Lyubomir Dimitrov et al. P-Type ATPase Apt1 of the fungal pathogen Cryptococcus neoformans is a lipid flippase of broad substrate specificity. J. Fungi, V.7, n. 843, p. 1–16, 2021.
dc.identifier2309-608X
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/50002
dc.identifier10.3390/jof7100843
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8883491
dc.descriptionLipid flippases of the P4-ATPase family are ATP-driven transporters that translocate lipids from the exoplasmic to the cytosolic leaflet of biological membranes. In the encapsulated fungal pathogen Cryptococcus neoformans, the P4-ATPase Apt1p is an important regulator of polysaccharide secretion and pathogenesis, but its biochemical characterization is lacking. Phylogenetic analysis revealed that Apt1p belongs to the subclade of P4A-ATPases characterized by the common requirement for a β-subunit. Using heterologous expression in S. cerevisiae, we demonstrate that Apt1p forms a heterodimeric complex with the C. neoformans Cdc50 protein. This association is required for both localization and activity of the transporter complex. Lipid flippase activity of the heterodimeric complex was assessed by complementation tests and uptake assays employing fluorescent lipids and revealed a broad substrate specificity, including several phospholipids, the alkylphospholipid miltefosine, and the glycolipids glucosyl- and galactosylceramide. Our results suggest that transbilayer lipid transport in C. neoformans is finely regulated to promote fungal virulence, which reinforces the potential of Apt1p as a target for antifungal drug development.
dc.formatapplication/pdf
dc.languagepor
dc.publisherMDPI
dc.rightsopen access
dc.subjectExpressão Heteróloga
dc.subjectCDC50
dc.subjectLipids
dc.subjectMembrane Transport Proteins
dc.subjectP-type ATPases
dc.subjectVirulence
dc.subjectLípidos
dc.subjectProteínas de Transporte de Membrana
dc.subjectATPasas Tipo P
dc.subjectVirulencia
dc.subjectLipides
dc.subjectProtéines de transport membranaire
dc.subjectP-type ATPases
dc.subjectVirulence
dc.subjectCryptococcus neoformans
dc.subjectLipídeos
dc.subjectProteínas de Membrana Transportadoras
dc.subjectATPases do Tipo-P
dc.subjectVirulência
dc.titleP-Type ATPase Apt1 of the fungal pathogen Cryptococcus neoformans is a lipid flippase of broad substrate specificity
dc.typeArticle


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