Biochimica et Biophysica Acta 2014-10-01

Phosphatidylinositol binding of Saccharomyces cerevisiae Pdr16p represents an essential feature of this lipid transfer protein to provide protection against azole antifungals.

Roman Holič, Zuzana Simová, Tim Ashlin, Vladimír Pevala, Katarína Poloncová, Dana Tahotná, Eva Kutejová, Shamshad Cockcroft, Peter Griač

文献索引：Biochim. Biophys. Acta 1842(10) , 1483-90, (2014)

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摘要

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. Copyright © 2014. Published by Elsevier B.V.