title: Pathogen-Related Yeast (PRY) proteins and members of the CAP superfamily are secreted sterol-binding proteins.
abstract: Sterols and related membrane-perturbing agents are subject to a quality control cycle. Compounds that fail to pass this control are acetylated and secreted into the culture media, whereas lipids that pass the cycle are deacetylated and retained within the cell. Here we describe the identification of a family of conserved proteins, the Pathogen-Related Yeast (PRY) proteins, as a class of sterol-binding proteins. Saccharomyces cerevisiae has three members of this family, two of which, Pry1 and Pry2, are secreted, whereas Pry3 is a cell wall-associated protein. Cells lacking both PRY1 and PRY2 have a complete block in secretion of the acetylated lipid and Pry1 and Pry2 proteins bind free cholesterol and cholesteryl acetate in vitro. PRY proteins belong to a large protein superfamily of unknown mode of action, the CAP protein superfamily [i.e. cysteine-rich secretory proteins (CRISP), antigen 5, and pathogenesis related 1 proteins]. The conserved CAP domain of Pry1 is necessary and sufficient for lipid export and sterol binding. Expression of a human CAP superfamily member, the cysteine-rich secretory protein 2 (CRISP2), rescues the phenotype of yeast mutants lacking Pry function and purified CRISP2 binds cholesterol in vitro, indicating that lipid binding is a conserved function of the CAP superfamily proteins.
authors.affiliation: Division of Biochemistry, Department of Biology,  University of Fribourg, 1700 Fribourg,  Switzerland.
authors.forename: Vineet
authors.initials: V
authors.lastname: Choudhary
authors.forename: Roger
authors.initials: R
authors.lastname: Schneiter
mesh_terms: D000107:Acetylation; D015153:Blotting, Western; D015815:Cell Adhesion Molecules; D002784:Cholesterol / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D002942:Circular Dichroism; D003001:Cloning, Molecular; D004591:Electrophoresis, Polyacrylamide Gel; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D005810:Multigene Family / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013261:Sterols / Q000378:metabolism*
chemical_list: C062621:CRISP2 protein, human; D015815:Cell Adhesion Molecules; D002788:Cholesterol Esters; D006023:Glycoproteins; C095462:PRY2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D013261:Sterols; D002784:Cholesterol; C060123:cholesterol acetate