A heterozygous defect for structurally altered pro-alpha 2 chain of type I procollagen in a mild variant of osteogenesis imperfecta. The altered structure decreases the thermal stability of procollagen and makes it resistant to procollagen N-proteinase.
A heterozygous defect for structurally altered pro-alpha 2 chain of type I procollagen in a mild variant of osteogenesis imperfecta. The altered structure decreases the thermal stability of procollagen and makes it resistant to procollagen N-proteinase.
复制标题
在成骨不全症的轻度变异中，I 型原胶原的 pro-α2 链结构改变的杂合缺陷。
DOI：
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发表时间：
1984
影响因子：
4.8
通讯作者：
D. Prockop
中科院分区：
文献类型：
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作者：
M. Sippola;S. Kaffe;D. Prockop
来自患有成骨不全的常染色体显性变异的先证者的培养皮肤成纤维细胞被发现合成大约等量的I型原胶原的正常pro-alpha 2(I)链和pro-alpha 2(I)链，当在十二烷基硫酸钠中进行聚丙烯酰胺凝胶电泳检查时，pro-alpha 2(I)链迁移得更快。结构改变存在于α2(I)-CB4中，这是一种含有α2链7-327位氨基酸残基的溴化氰片段，并且似乎缺失了约30个氨基酸。与由相同成纤维细胞合成的正常pro-α1(I)链相关的明显缺失的pro-α2(I)链并形成三螺旋I型原胶原。前胶原三聚体中改变的前 α2 链的存在对分子的物理性质有两个影响。一种是降低蛋白质的热稳定性，这通过 37 摄氏度下的蛋白水解抗性和圆二色性测定的螺旋到卷曲的转变来判断。第二个结果是使含有缩短的原α2(I)链的I型原胶原能够抵抗原胶原N-蛋白酶的消化。对数据最简单的解释是，一半的 pro-alpha 2(I) 链的明显缺失导致 I 型原胶原的 N 末端区域部分展开，从而阻止了原胶原 N-蛋白酶对蛋白质的加工。
Cultured skin fibroblasts from a proband with an autosomal dominant variant of osteogenesis inperfecta were found to synthesize approximately equal amounts of normal pro-alpha 2(I) chains of type I procollagen and pro-alpha 2(I) chains which migrated more rapidly when examined by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. The structural alteration was present in alpha 2(I)-CB4, a cyanogen bromide fragment containing amino acid residues 7-327 of the alpha 2 chain, and it appeared to be a deletion of about 30 amino acids. The pro-alpha 2(I) chains with the apparent deletion associated with normal pro-alpha 1(I) chains synthesized by the same fibroblasts and formed triple-helical type I procollagen. The presence of the altered pro-alpha 2 chains in trimers of procollagen had two consequences in terms of the physical properties of the molecule. One was to decrease the thermal stability of the protein as judged by resistance to proteolysis at 37 degrees C and by the helix to coil transition as assayed by circular dichroism. The second consequence was to make type I procollagen containing the shortened pro-alpha 2(I) chains resistant to digestion by procollagen N-proteinase. The simplest explanation for the data is that the apparent deletion in half the pro-alpha 2(I) chains produced a partial unfolding of the N-terminal region of type I procollagen which prevented processing of the protein by procollagen N-proteinase.