Osteogenesis imperfecta. The position of substitution for glycine by cysteine in the triple helical domain of the pro alpha 1(I) chains of type I collagen determines the clinical phenotype.
Osteogenesis imperfecta. The position of substitution for glycine by cysteine in the triple helical domain of the pro alpha 1(I) chains of type I collagen determines the clinical phenotype.
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成骨不全。
DOI：
10.1172/jci114286
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Byers,PH
中科院分区：
文献类型：
--
作者：
Starman,BJ;Eyre,D;Charbonneau,H;Harrylock,M;Weis,MA;Weiss,L;GrahamJr,JM;Byers,PH
从三个患有成骨不全症 (OI) 的个体中生长的皮肤成纤维细胞各自合成了一群正常的 I 型胶原分子和其他分子，这些分子具有一个或两个 α 1(I) 链，这些链在三螺旋结构域内包含半胱氨酸残基，该区域通常排除半胱氨酸。患者有非常不同的表型。一名 I 型 OI 患者的 α1(I) 链群体中，三螺旋第 94 位的甘氨酸被半胱氨酸取代；一名 III 型 OI 患者的 α 1(I) 链群体中，三螺旋第 526 位的甘氨酸被半胱氨酸取代；第三名 II 型 OI 患者在 α 1(I) 链的 718 位上用半胱氨酸取代了甘氨酸。对于所有三名患者，含有两条突变链的分子形成了链间、分子内二硫键，虽然热变性稳定性不如正常分子，但它们比仅含有一条突变链的分子更稳定。这些发现表明，α 1(I) 链三螺旋结构域内甘氨酸的取代并不总是致命的，并且它们的表型效应很大程度上取决于取代残基的性质及其在链中的位置。
Skin fibroblasts grown from three individuals with osteogenesis imperfecta (OI) each synthesized a population of normal type I collagen molecules and additional molecules that had one or two alpha 1(I) chains that contained a cysteine residue within the triple-helical domain, a region from which cysteine normally is excluded. The patients had very different phenotypes. One patient with OI type I had a population of alpha 1(I) chains in which glycine at position 94 of the triple helix was substituted by cysteine; a patient with OI type III had a population of alpha 1(I) chains in which glycine at position 526 of the triple helix was substituted by cysteine; and the third patient, with OI type II, had a cysteine for glycine substitution at position 718 of the alpha 1(I) chain. From all three patients, molecules that contained two mutant chains formed interchain, intramolecular disulfide bonds, and although less stable to thermal denaturation than normal molecules, they were more stable than molecules that contained only a single mutant chain. These findings indicate that substitutions for glycine within the triple-helical domain of the alpha 1(I) chain are not invariably lethal and that their phenotypic effect largely depends on the nature of the substituting residue and its location in the chain.Images