Colige A, Li S W, Sieron A L, Nusgens B V, Prockop D J, Lapière C M
Laboratory of Connective Tissues Biology, University of Liege, Belgium.
Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2374-9. doi: 10.1073/pnas.94.6.2374.
Procollagen N-proteinase (EC 3.4.24.14) cleaves the amino-propeptides in the processing of type I and type II procollagens to collagens. Deficiencies of the enzyme cause dermatosparaxis in cattle and sheep, and they cause type VIIC Ehlers-Danlos syndrome in humans, heritable disorders characterized by accumulation of pNcollagen and severe skin fragility. Amino acid sequences for the N-proteinase were used to obtain cDNAs from bovine skin. Three overlapping cDNAs had an ORF coding for a protein of 1205 residues. Mammalian cells stably transfected with a complete cDNA secreted an active recombinant enzyme that specifically cleaved type I procollagen. The protein contained zinc-binding sequences of the clan MB of metallopeptidases that includes procollagen C-proteinase/BMP-1. The protein also contained four repeats that are homologous to domains found in thrombospondins and in properdin and that can participate in complex intermolecular interactions such as activation of latent forms of transforming growth factor beta or the binding to sulfatides. Therefore, the enzyme may play a role in development that is independent of its role in collagen biosynthesis. This hypothesis was supported by the observation that in some tissues the levels of mRNA for the enzyme are disproportionately high relative to the apparent rate of collagen biosynthesis.
前胶原N蛋白酶（EC 3.4.24.14）在I型和II型前胶原加工成胶原蛋白的过程中切割氨基前肽。该酶的缺乏会导致牛和羊的皮肤松弛症，在人类中会导致VII型埃勒斯-当洛综合征，这些遗传性疾病的特征是前胶原N端肽（pNcollagen）积累和严重的皮肤脆弱性。利用N蛋白酶的氨基酸序列从牛皮肤中获得了cDNA。三个重叠的cDNA具有一个编码1205个残基蛋白质的开放阅读框（ORF）。用完整cDNA稳定转染的哺乳动物细胞分泌一种活性重组酶，该酶能特异性切割I型前胶原。该蛋白质含有金属肽酶MB家族的锌结合序列，其中包括前胶原C蛋白酶/BMP-1。该蛋白质还含有四个与血小板反应蛋白和备解素中发现的结构域同源的重复序列，这些重复序列可参与复杂的分子间相互作用，如转化生长因子β潜在形式的激活或与硫脂的结合。因此，该酶可能在发育过程中发挥作用，而与其在胶原蛋白生物合成中的作用无关。这一假设得到了以下观察结果的支持：在某些组织中，该酶的mRNA水平相对于明显的胶原蛋白生物合成速率过高。
