Release of signal peptide fragments into the cytosol requires cleavage in the transmembrane region by a protease activity that is specifically blocked by a novel cysteine protease inhibitor
Release of signal peptide fragments into the cytosol requires cleavage in the transmembrane region by a protease activity that is specifically blocked by a novel cysteine protease inhibitor
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DOI：
10.1074/jbc.m005980200
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发表时间：
2000-10-06
影响因子：
4.8
通讯作者：
Martoglio, B
中科院分区：
文献类型：
--
作者：
Weihofen, A;Lemberg, MK;Martoglio, B
分泌蛋白和膜蛋白的信号肽是前体蛋白插入内质网膜后通过蛋白水解加工而产生的。释放的信号肽可以进一步加工，产生的n端片段被释放到细胞质中，在那里它们可能与靶蛋白如钙调蛋白相互作用。我们发现信号肽的加工需要一种不同于信号肽酶的蛋白酶活性，这种活性被一种新开发的半胱氨酸蛋白酶抑制剂1,3-二-（n -羧基苯甲酰-l -亮氨酸-l -亮氨酸）氨基丙酮(（Z-LL)(2)酮）特异性抑制。抑制剂研究表明，最终的（Z-LL）(2)酮敏感切割事件发生在信号肽的疏水跨膜区域内，从而促进n端片段释放到细胞质中。
Signal peptides of secretory and membrane proteins are generated by proteolytic processing of precursor proteins after insertion into the endoplasmic reticulum membrane. Liberated signal peptides can be further processed, and the resulting N-terminal fragments are released toward the cytosol, where they may interact with target proteins like calmodulin. We show here that the processing of signal peptides requires a protease activity distinct from signal peptidase, This activity is inhibited specifically with a newly developed cysteine protease inhibitor, 1,3-di-(N-carboxybenzoyl-L-leucyl-L-leucyl)amino acetone ((Z-LL)(2) ketone). Inhibitor studies revealed that the final, (Z-LL)(2) ketone sensitive cleavage event occurs within the hydrophobic transmembrane region of the signal peptide, thus promoting the release of an N-terminal fragment into the cytosol.