脱落的弗林蛋白酶：切割决定簇的定位及其C末端的鉴定。
'Shed' furin: mapping of the cleavage determinants and identification of its C-terminus.
作者信息
Plaimauer B, Mohr G, Wernhart W, Himmelspach M, Dorner F, Schlokat U
机构信息
Biomedical Research Center, Hyland-Immuno Division, Baxter Healthcare, Uferstr. 15, 2304 Orth/Donau, Austria.
出版信息
Biochem J. 2001 Mar 15;354(Pt 3):689-95. doi: 10.1042/0264-6021:3540689.
Abstract
The human endoprotease furin is involved in the proteolytic maturation of the precursor molecules of a wide variety of bioactive proteins. Despite its localization in the membranes of the trans-Golgi system by means of a transmembrane domain, it has repeatedly been reported to form a C-terminally truncated, naturally secreted form referred to as 'shed' furin. In order to identify the cleavage site, internal deletion mutants of increasing size, N-terminal to Leu(708), and subsequently individual amino acid substitutions were introduced, and Arg(683) was identified as the prime determinant for shedding. MS analysis determined Ser(682) as the C-terminus of shed furin, suggesting that monobasic cleavage may occur N-terminal to Arg(683). Alteration of Arg(683) directs the shedding mechanism to alternative cleaving sites previously unused.
摘要
人内切蛋白酶弗林蛋白酶参与多种生物活性蛋白前体分子的蛋白水解成熟过程。尽管它通过跨膜结构域定位于反式高尔基体系统的膜上，但多次有报道称它会形成一种C末端截短的、自然分泌的形式，即“脱落型”弗林蛋白酶。为了确定切割位点，引入了一系列大小递增的内部缺失突变体（位于Leu(708)的N端），随后进行单个氨基酸替换，结果确定Arg(683)是脱落的主要决定因素。质谱分析确定Ser(682)为脱落型弗林蛋白酶的C末端，这表明单碱基切割可能发生在Arg(683)的N端。Arg(683)的改变会使脱落机制导向以前未使用过的替代切割位点。
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