title: Phosphatidylinositol binding of Saccharomyces cerevisiae Pdr16p represents an essential feature of this lipid transfer protein to provide protection against azole antifungals.
abstract: 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 Pdr16p(E235A, 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 Pdr16p(E235A, K267A) mutant, to bind sterol molecules, is observed.
authors: Department of Membrane Biochemistry, Institute of Animal Biochemistry and Genetics, Slovak Academy of Sciences, 900 28 Ivanka pri Dunaji, Slovakia.
authors: Roman
authors: R
authors: Holič
authors: Department of Membrane Biochemistry, Institute of Animal Biochemistry and Genetics, Slovak Academy of Sciences, 900 28 Ivanka pri Dunaji, Slovakia.
authors: Zuzana
authors: Z
authors: Simová
authors: Department of Neuroscience, Physiology and Pharmacology, Division of Biosciences, University College London, London WC1E 6JJ, United Kingdom.
authors: Tim
authors: T
authors: Ashlin
authors: Department of Biochemistry and Structural Biology, Institute of Molecular Biology, Slovak Academy of Sciences, 845 51 Bratislava, Slovakia.
authors: Vladimír
authors: V
authors: Pevala
authors: Department of Membrane Biochemistry, Institute of Animal Biochemistry and Genetics, Slovak Academy of Sciences, 900 28 Ivanka pri Dunaji, Slovakia.
authors: Katarína
authors: K
authors: Poloncová
authors: Department of Membrane Biochemistry, Institute of Animal Biochemistry and Genetics, Slovak Academy of Sciences, 900 28 Ivanka pri Dunaji, Slovakia.
authors: Dana
authors: D
authors: Tahotná
authors: Department of Biochemistry and Structural Biology, Institute of Molecular Biology, Slovak Academy of Sciences, 845 51 Bratislava, Slovakia.
authors: Eva
authors: E
authors: Kutejová
authors: Department of Neuroscience, Physiology and Pharmacology, Division of Biosciences, University College London, London WC1E 6JJ, United Kingdom.
authors: Shamshad
authors: S
authors: Cockcroft
authors: Department of Membrane Biochemistry, Institute of Animal Biochemistry and Genetics, Slovak Academy of Sciences, 900 28 Ivanka pri Dunaji, Slovakia. Electronic address: Peter.Griac@savba.sk.
authors: Peter
authors: P
authors: Griač
keywords: Azole resistance; Lipid binding; SFH3; Saccharomyces cerevisiae; Sterol metabolism