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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Pathogen-Related Yeast (PRY) proteins and members of the CAP superfamily are secreted sterol-binding proteins
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Pathogen-Related Yeast (PRY) proteins and members of the CAP superfamily are secreted sterol-binding proteins

机译:病原相关酵母(PRY)蛋白和CAP超家族成员是固醇结合蛋白

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摘要

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 Pry 1 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.
机译:甾醇和相关的膜干扰剂要经过质量控制周期。未能通过此控制的化合物被乙酰化并分泌到培养基中,而通过循环的脂质则被脱乙酰化并保留在细胞内。在这里,我们描述了作为一类固醇结合蛋白的保守蛋白家族(病原相关酵母(PRY)蛋白)的鉴定。酿酒酵母具有该家族的三个成员,其中两个被分泌,Pry1和Pry2,而Pry3是与细胞壁相关的蛋白质。缺少PRY1和PRY2的细胞在乙酰化脂质的分泌中具有完全的阻滞作用,并且Pry1和Pry2蛋白在体外结合游离胆固醇和乙酸胆固醇酯。 PRY蛋白属于作用模式未知的大蛋白超家族,即CAP蛋白超家族。富含半胱氨酸的分泌蛋白(CRISP),抗原5和与发病相关的1种蛋白]。 Pry 1的保守CAP结构域对于脂质输出和固醇结合而言是必要和充分的。人CAP超家族成员富含半胱氨酸的分泌蛋白2(CRISP2)的表达拯救了缺乏Pry功能的酵母突变体的表型,纯化的CRISP2在体外结合胆固醇,表明脂质结合是CAP超家族蛋白的保守功能。

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