Phosphatidylinositol binding of Saccharomyces cerevisiae Pdr16p represents an essential feature of this lipid transfer protein to provide protection against azole antifungals
| Autor: | Roman, Holič, Zuzana, Simová, Tim, Ashlin, Vladimír, Pevala, Katarína, Poloncová, Dana, Tahotná, Eva, Kutejová, Shamshad, Cockcroft, Peter, Griač |
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| Rok vydání: | 2014 |
| Předmět: |
LPC
Lysophosphocholine PC Phosphatidylcholine PS Phosphatidylserine Saccharomyces cerevisiae Article Osh oxysterol-binding homology PI3P Phosphatidylinositol (3) phosphate PI4 5P2 Phosphatidylinositol (4 5) bisphosphate PI3 5P2 Phosphatidylinositol (3 5) bisphosphate HL60 human promyelocytic leukemia cells Lipid binding MIC minimal inhibitory concentration PI4P Phosphatidylinositol (4) phosphate PE Phosphatidylethanolamine PI5P Phosphatidylinositol (5) phosphate PI Phosphatidylinositol PI3 4 5P3 Phosphatidylinositol (3 4 5) trisphosphate PI3 4P2 Phosphatidylinositol (3 4) bisphosphate PITP phosphatidylinositol transfer protein Sterol metabolism S1P Sphingosine 1-Phosphate NPPMs nitrophenyl(4-(2-methoxyphenyl)piperazin-1yl)methanone Azole resistance PA Phosphatidic acid LPA Lysophosphatidic acid SFH3 |
| Zdroj: | Biochimica et Biophysica Acta |
| ISSN: | 0006-3002 |
| Popis: | Pdr16p is considered a factor of clinical azole resistance in fungal pathogens. The most distinct phenotype of yeast cells lacking Pdr16p is their increased susceptibility to azole and morpholine antifungals. Pdr16p (also known as Sfh3p) of Saccharomyces cerevisiae belongs to the Sec14 family of phosphatidylinositol transfer proteins. It facilitates transfer of phosphatidylinositol (PI) between membrane compartments in in vitro systems. We generated Pdr16pE235A, K267A mutant defective in PI binding. This PI binding deficient mutant is not able to fulfill the role of Pdr16p in protection against azole and morpholine antifungals, providing evidence that PI binding is critical for Pdr16 function in modulation of sterol metabolism in response to these two types of antifungal drugs. A novel feature of Pdr16p, and especially of Pdr16pE235A, K267A mutant, to bind sterol molecules, is observed. Highlights • Yeast Pdr16p binds phosphatidylinositol (PI) and cholesterol in lipid binding assay. • Pdr16pE235A, K267A is defective in PI binding, it binds sterols instead of PI. • Pdr16p defective in PI binding does not fulfill Pdr16p role in azole protection. • PI binding of Pdr16p is critical for its function. |
| Databáze: | OpenAIRE |
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