Prostate secretory protein 94 inhibits sterol binding and export by the mammalian CAP protein CRISP2 in a calcium-sensitive manner.
Prostate secretory protein 94 inhibits sterol binding and export by the mammalian CAP protein CRISP2 in a calcium-sensitive manner.
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前列腺分泌蛋白 94 以钙敏感方式抑制哺乳动物 CAP 蛋白 CRISP2 的甾醇结合和输出。
DOI：
10.1016/j.jbc.2022.101600
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Schneiter R
中科院分区：
文献类型：
--
作者：
El Atab O;Kocabey AE;Asojo OA;Schneiter R
CAP蛋白超家族成员存在于所有生命王国中，并涉及许多不同的过程，包括病原体防御、免疫逃避、精子成熟和癌症进展。大多数CAP蛋白是分泌糖蛋白，并共享一个独特的保守αβα夹心折叠。然而，这类蛋白质的确切作用方式仍然难以捉摸。酿酒酵母（Saccharomyces cerevisiae）有三个CAP家族成员，称为酵母相关病原体（Pry）。我们之前已经证明Pry1和Pry2在体内输出甾醇，并在体外结合甾醇。酵母Pry蛋白的这种甾醇结合和输出功能在哺乳动物CRISP蛋白和其他CAP超家族成员中是保守的。CRISP3是人类精浆中丰富的一种蛋白，与精浆中的另一种主要蛋白成分前列腺分泌蛋白（PSP94）相互作用。本文研究了CRISP蛋白与PSP94之间的相互作用是否会影响CAP家族成员的固醇结合功能。在体外实验中，我们发现PSP94与CAP蛋白的共表达破坏了它们的甾醇输出功能，PSP94与CAP蛋白的相互作用抑制了甾醇的结合。此外，影响PSP94-CRISP2异质复合体形成的突变恢复了甾醇结合。有趣的是，我们发现PSP94与CRISP2的相互作用对高钙浓度敏感。观察到PSP94以钙依赖的方式调节CRISP2的甾醇结合功能，这对PSP94和CRISP2在前列腺生理和前列腺癌进展中的作用具有潜在的意义。
Members of the CAP protein superfamily are present in all kingdoms of life and have been implicated in many different processes, including pathogen defense, immune evasion, sperm maturation, and cancer progression. Most CAP proteins are secreted glycoproteins and share a unique conserved αβα sandwich fold. The precise mode of action of this class of proteins, however, has remained elusive. Saccharomyces cerevisiae has three CAP family members, termed pathogen related in yeast (Pry). We have previously shown that Pry1 and Pry2 export sterols in vivo and that they bind sterols in vitro. This sterol binding and export function of yeast Pry proteins is conserved in the mammalian CRISP proteins and other CAP superfamily members. CRISP3 is an abundant protein of the human seminal plasma and interacts with prostate secretory protein of 94 amino acids (PSP94), another major protein component in the seminal plasma. Here we examine whether the interaction between CRISP proteins and PSP94 affects the sterol binding function of CAP family members. We show that coexpression of PSP94 with CAP proteins in yeast abolished their sterol export function and the interaction between PSP94 and CAP proteins inhibits sterol binding in vitro. In addition, mutations that affect the formation of the PSP94–CRISP2 heteromeric complex restore sterol binding. Of interest, we found the interaction of PSP94 with CRISP2 is sensitive to high calcium concentrations. The observation that PSP94 modulates the sterol binding function of CRISP2 in a calcium-dependent manner has potential implications for the role of PSP94 and CRISP2 in prostate physiology and progression of prostate cancer.
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影响因子：
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