Author | Stanchev, Lyubomir Dimitrov | |
Author | Rizzo, Juliana | |
Author | Peschel, Rebecca | |
Author | Pazurek, Lilli A. | |
Author | Bredegaard, Lasse | |
Author | Veit, Sarina | |
Author | Laerbusch, Sabine | |
Author | Rodrigues, Marcio Lourenço | |
Author | López-Marqués, Rosa L. | |
Author | Pomorski, Thomas Günther | |
Access date | 2021-11-24T12:32:12Z | |
Available date | 2021-11-24T12:32:12Z | |
Document date | 2021 | |
Citation | STANCHEV, 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. | pt_BR |
ISSN | 2309-608X | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/50002 | |
Language | por | pt_BR |
Publisher | MDPI | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Expressão Heteróloga | pt_BR |
Subject in Portuguese | CDC50 | pt_BR |
Title | P-Type ATPase Apt1 of the fungal pathogen Cryptococcus neoformans is a lipid flippase of broad substrate specificity | pt_BR |
Type | Article | pt_BR |
DOI | 10.3390/jof7100843 | |
Abstract | Lipid 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. | pt_BR |
Affilliation | Department of Molecular Biochemistry. Faculty of Chemistry and Biochemistry. Ruhr University Bochum. Bochum, Germany. / Department of Plant and Environmental Sciences. University of Copenhagen. Frederiksberg, Denmark. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Rio de Janeiro, RJ, Brasil. / Institut Pasteur. Département de Mycologie. Unité Biologie des ARN des Pathogènes Fongiques. Paris, France. | pt_BR |
Affilliation | Department of Molecular Biochemistry. Faculty of Chemistry and Biochemistry. Ruhr University Bochum. Bochum, Germany. | pt_BR |
Affilliation | Department of Molecular Biochemistry. Faculty of Chemistry and Biochemistry. Ruhr University Bochum. Bochum, Germany. | pt_BR |
Affilliation | Department of Plant and Environmental Sciences. University of Copenhagen. Frederiksberg, Denmark. | pt_BR |
Affilliation | Department of Molecular Biochemistry. Faculty of Chemistry and Biochemistry. Ruhr University Bochum. Bochum, Germany. | pt_BR |
Affilliation | Department of Molecular Biochemistry. Faculty of Chemistry and Biochemistry. Ruhr University Bochum. Bochum, Germany. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Rio de Janeiro, RJ, Brasil. / Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil. | pt_BR |
Affilliation | Department of Plant and Environmental Sciences. University of Copenhagen. Frederiksberg, Denmark. | pt_BR |
Affilliation | Department of Molecular Biochemistry. Faculty of Chemistry and Biochemistry. Ruhr University Bochum. Bochum, Germany. / Department of Plant and Environmental Sciences. University of Copenhagen. Frederiksberg, Denmark. | pt_BR |
Subject | Lipids | pt_BR |
Subject | Membrane Transport Proteins | pt_BR |
Subject | P-type ATPases | pt_BR |
Subject | Virulence | pt_BR |
Subject in Spanish | Lípidos | pt_BR |
Subject in Spanish | Proteínas de Transporte de Membrana | pt_BR |
Subject in Spanish | ATPasas Tipo P | pt_BR |
Subject in Spanish | Virulencia | pt_BR |
Subject in French | Lipides | pt_BR |
Subject in French | Protéines de transport membranaire | pt_BR |
Subject in French | P-type ATPases | pt_BR |
Subject in French | Virulence | pt_BR |
DeCS | Cryptococcus neoformans | pt_BR |
DeCS | Lipídeos | pt_BR |
DeCS | Proteínas de Membrana Transportadoras | pt_BR |
DeCS | ATPases do Tipo-P | pt_BR |
DeCS | Virulência | pt_BR |