Fertala A, Westerhausen A, Morris G, Rooney J E, Prockop D J
Department of Biochemistry and Molecular Biology, Jefferson Institute of Molecular Medicine, jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
Biochem J. 1993 Jan 1;289 ( Pt 1)(Pt 1):195-9. doi: 10.1042/bj2890195.
Cultured skin fibroblasts were examined from two probands with type II (lethal) osteogenesis imperfecta. One proband had a single base mutation which converted the glycine codon at position alpha 1-244 in the alpha 1(I) chain of procollagen I into a cysteine codon whereas the other had a similar mutation that converted the glycine codon at position alpha 2-787 of the alpha 2(I) chain into a cysteine codon. Both mutations produced post-translational overmodification of procollagen I. The Cys alpha 1-244 mutation, however, had a minimal effect on the thermal stability or secretion of the protein whereas the Cys alpha 2-787 mutation markedly decreased the thermal stability and, apparently as a result, essentially none of the mutated protein was secreted. The results provide clear exceptions to two previous generalizations about the position-specificity of glycine substitutions in procollagen I.
对两名患有II型（致死性）成骨不全症的先证者的培养皮肤成纤维细胞进行了检查。一名先证者有一个单碱基突变，该突变将原胶原I的α1(I)链中α1-244位的甘氨酸密码子转换为半胱氨酸密码子，而另一名先证者有类似的突变，将α2(I)链中α2-787位的甘氨酸密码子转换为半胱氨酸密码子。这两种突变都导致了原胶原I的翻译后过度修饰。然而，Cysα1-244突变对该蛋白的热稳定性或分泌影响极小，而Cysα2-787突变则显著降低了热稳定性，显然因此基本上没有突变蛋白被分泌。这些结果为之前关于原胶原I中甘氨酸替代的位置特异性的两个普遍观点提供了明确的反例。
