Saposins: structure, function, distribution, and molecular genetics.
Saposins: structure, function, distribution, and molecular genetics.
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DOI：
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发表时间：
1992-09
影响因子：
6.5
通讯作者：
Yasuo Kishimoto;Masao Hiraiwa;John S. O'brien
中科院分区：
文献类型：
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作者：
Yasuo Kishimoto;Masao Hiraiwa;John S. O'brien
Saposin A、B、C 和 D 是源自常见前体蛋白 prosaposin 的小型热稳定性糖蛋白。这些成熟的saposin以及prosaposin激活几种参与各种鞘脂代谢的溶酶体水解酶。所有四种皂苷在结构上彼此相似，包括在相同位置放置六个半胱氨酸、一个糖基化位点和保守脯氨酸。尽管结构相似，但鞘脂水解酶的特异性和激活模式在各个皂苷之间是不同的。皂苷似乎是溶酶体蛋白，对溶酶体水解酶发挥作用。 Prosaposin 是一种 70 kDa 的糖蛋白，包含四个串联结构域，每个结构域对应一个 Saposin。显然是在溶酶体中，前皂苷被蛋白水解加工成皂苷 A、B、C 和 D。然而，prosaposin 也作为一种不可进入溶酶体的完整膜蛋白存在，并且以未切割的形式存在于许多生物液体中，例如精浆、人乳和脑脊液，在这些生物液体中它似乎具有不同的功能。 saposin 的生理意义通过其在溶酶体贮积病患者的组织中的积累以及由于 prosaposin 基因突变而发生的鞘脂沉积症而得到强调。本综述概述了这些皂苷蛋白的出现、结构和功能。
Saposins A, B, C, and D are small heat-stable glycoproteins derived from a common precursor protein, prosaposin. These mature saposins, as well as prosaposin, activate several lysosomal hydrolases involved in the metabolism of various sphingolipids. All four saposins are structurally similar to one another including placement of six cysteines, a glycosylation site, and conserved prolines in identical positions. In spite of the structural similarities, the specificity and mode of activation of sphingolipid hydrolases differs among individual saposins. Saposins appear to be lysosomal proteins, exerting their action upon lysosomal hydrolases. Prosaposin is a 70 kDa glycoprotein containing four domains, one for each saposin, placed in tandem. Prosaposin is proteolytically processed to saposins A, B, C and D, apparently within lysosomes. However, prosaposin also exists as an integral membrane protein not destined for lysosomal entry and exists uncleaved in many biological fluids such as seminal plasma, human milk, and cerebrospinal fluid, where it appears to have a different function. The physiological significance of saposins is underlined by their accumulation in tissues of lysosomal storage disease patients and the occurrence of sphingolipidosis due to mutations in the prosaposin gene. This review presents an overview of the occurrence, structure and function of these saposin proteins.