Voss Matthias, Schröder Bernd, Fluhrer Regina
Adolf Butenandt Institute for Biochemistry, Ludwig-Maximilians University Munich, Schillerstr. 44, 80336 Munich, Germany.
Biochim Biophys Acta. 2013 Dec;1828(12):2828-39. doi: 10.1016/j.bbamem.2013.03.033.
Signal peptide peptidase (SPP) and the homologous SPP-like (SPPL) proteases SPPL2a, SPPL2b, SPPL2c and SPPL3 belong to the family of GxGD intramembrane proteases. SPP/SPPLs selectively cleave transmembrane domains in type II orientation and do not require additional co-factors for proteolytic activity. Orthologues of SPP and SPPLs have been identified in other vertebrates, plants, and eukaryotes. In line with their diverse subcellular localisations ranging from the ER (SPP, SPPL2c), the Golgi (SPPL3), the plasma membrane (SPPL2b) to lysosomes/late endosomes (SPPL2a), the different members of the SPP/SPPL family seem to exhibit distinct functions. Here, we review the substrates of these proteases identified to date as well as the current state of knowledge about the physiological implications of these proteolytic events as deduced from in vivo studies. Furthermore, the present knowledge on the structure of intramembrane proteases of the SPP/SPPL family, their cleavage mechanism and their substrate requirements are summarised. This article is part of a Special Issue entitled: Intramembrane Proteases.
信号肽肽酶（SPP）以及同源的类信号肽肽酶（SPPL）蛋白酶SPPL2a、SPPL2b、SPPL2c和SPPL3属于GxGD跨膜蛋白酶家族。SPP/SPPLs选择性切割II型方向的跨膜结构域，且蛋白水解活性不需要额外的辅助因子。在其他脊椎动物、植物和真核生物中已鉴定出SPP和SPPLs的直系同源物。鉴于它们在亚细胞定位上的多样性，从内质网（SPP、SPPL2c）、高尔基体（SPPL3）、质膜（SPPL2b）到溶酶体/晚期内体（SPPL2a），SPP/SPPL家族的不同成员似乎具有不同的功能。在此，我们综述了迄今为止已鉴定出的这些蛋白酶的底物，以及从体内研究推断出的关于这些蛋白水解事件生理意义的当前知识状态。此外，还总结了目前关于SPP/SPPL家族跨膜蛋白酶的结构、切割机制及其底物需求的知识。本文是名为“跨膜蛋白酶”的特刊的一部分。
