Proteinases of the bone morphogenetic protein-1 family convert procollagen VII to mature anchoring fibril collagen
Proteinases of the bone morphogenetic protein-1 family convert procollagen VII to mature anchoring fibril collagen
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DOI：
10.1074/jbc.m203247200
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发表时间：
2002-07-19
影响因子：
4.8
通讯作者：
Bruckner-Tuderman, L
中科院分区：
文献类型：
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作者：
Rattenholl, A;Pappano, WN;Bruckner-Tuderman, L
胶原蛋白VII是皮肤中真皮-表皮连接处的锚定原纤维的主要结构组分。它由角质形成细胞作为前体VII型前胶原分泌，并在锚定原纤维聚合期间加工成成熟胶原。我们表明，骨形态发生蛋白-1（BMP-1），它具有前胶原C-蛋白酶活性，切割的C-末端前肽从人前胶原VII。切割发生在NC-2结构域内的BMP-1共有切割位点SYAA向下箭头DTAG处。哺乳动物tolloid-like（mTLL）-1和-2，两个其他蛋白酶的astacin酶家族，能够处理前胶原VII在同一网站在体外。免疫组织化学和遗传学证据支持参与这些酶在体内切割VII型前胶原。BMP-1和mTLL-1都在皮肤和培养的皮肤细胞中表达。人COL 7A 1基因8523 del 14的天然缺失与营养不良性大疱性表皮病相关，并消除了BMP-1共有序列，消除了VII型前胶原的加工，并在突变型皮肤中在真皮-表皮连接处积累了VII型前胶原。另一方面，基因敲除小鼠胚胎皮肤中BMP-1的缺乏并不能阻止VII型前胶原向成熟胶原的加工，这表明mTLL-1和/或mTLL-2可以在原位VII型前胶原的加工中替代BMP-1。
Collagen VII is the major structural component of the anchoring fibrils at the dermal-epidermal junction in the skin. It is secreted by keratinocytes as a precursor, procollagen VII, and processed into mature collagen during polymerization of the anchoring fibrils. We show that bone morphogenetic protein-1 (BMP-1), which exhibits procollagen C-proteinase activity, cleaves the C-terminal propeptide from human procollagen VII. The cleavage occurs at the BMP-1 consensus cleavage site SYAA down arrow DTAG within the NC-2 domain. Mammalian tolloid-like (mTLL)-1 and -2, two other proteases of the astacin enzyme family, were able to process procollagen VII at the same site in vitro. Immunohistochemical and genetic evidence supported the involvement of these enzymes in cleaving type VII procollagen in vivo. Both BMP-1 and mTLL-1 are expressed in the skin and in cultured cutaneous cells. A naturally occurring deletion in the human COL7A1 gene, 8523del14, which is associated with dystrophic epidermolysis bullosa and eliminates the BMP-1 consensus sequence, abolished processing of procollagen VII, and in mutant skin procollagen VII accumulated at the dermal-epidermal junction. On the other hand, deficiency of BMP-1 in the skin of knockout mouse embryos did not prevent processing of procollagen VII to mature collagen, suggesting that mTLL-1 and/or mTLL-2 can substitute for BMP-1 in the processing of procollagen VII in situ.