SUBTLE STRUCTURAL ALTERATIONS IN THE CHAINS OF TYPE-I PROCOLLAGEN PRODUCE OSTEOGENESIS IMPERFECTA TYPE-II
SUBTLE STRUCTURAL ALTERATIONS IN THE CHAINS OF TYPE-I PROCOLLAGEN PRODUCE OSTEOGENESIS IMPERFECTA TYPE-II
复制标题
DOI：
10.1038/316363a0
复制
发表时间：
1985-01-01
期刊：
影响因子：
64.8
通讯作者：
BYERS, PH
中科院分区：
文献类型：
--
作者：
BONADIO, J;BYERS, PH
虽然围产期致死性的成骨不全（II型OI）偶尔是由编码I型胶原2 -5的基因内的大的重排引起的，但大多数突变是非常微妙的。人类胶原蛋白基因的复杂性6排除了克隆和测序每个患者的每个基因，因此我们开发了一种在蛋白质水平定位突变的方法。我们在这里报告，从15个婴儿与II型OI培养的细胞合成正常的I型前胶原和一种不稳定，分泌不良和过度修饰的形式。不同菌株的异常前胶原有不同程度的过度修饰。我们观察到的过度修饰模式最好解释为破坏proα链的Gly-X-Y序列的突变，从而改变三螺旋从COOH末端到NH 2末端的增殖速率7。因此，给定的突变允许在分子NH 2-末端中的所有三条链过度修饰到其在三螺旋中的位置。
Although the perinatal lethal form1of osteogenesis imperfecta (OI type II) occasionally results from large rearrangements within the genes encoding type I collagen2–5, most mutations are far more subtle. The complexity of the human collagen genes6precludes cloning and sequencing each gene from every patient, and we have therefore developed an approach to localizing mutations at the protein level. We report here that cells cultured from 15 infants with OI type II synthesized both normal type I procollagen and a form that was unstable, poorly secreted and excessively modified. Abnormal procollagen from different strains was overmodified to different extents. The patterns of overmodification we observed are best explained by mutations that disrupt the Gly-X-Y sequence of proαchains, and thus alter the rate of propagation of triple helix from COOH-terminus to NH2-terminus7. As a consequence, a given mutation allows overmodification of all three chains in a molecule NH2-terminal to its position in the triple helix.