Simons R, Riordan J R
Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
J Neurochem. 1990 Mar;54(3):1079-81. doi: 10.1111/j.1471-4159.1990.tb02360.x.
Several genetic disorders that occur in animals and in humans result in an inability to synthesize normal myelin. Some of these disorders are inherited in an X-linked manner. The localization of the myelin proteolipid protein (PLP) gene to the X chromosome has directed the study of X-linked myelination disorders toward PLP. The myelin-deficient rat is one such X-linked dysmyelinating mutant. From a cDNA library constructed from myelin-deficient rat brain mRNA, we have isolated and sequenced cDNAs corresponding to PLP and its alternatively spliced isoform, DM-20. An A to C transition was detected in these cDNAs, which results in a threonine to proline change at amino acid 74 in both PLP and DM-20. No other substitutions were seen in the cDNA sequences. Polymerase chain reaction amplification and sequencing of the corresponding genomic regions were used to confirm the single base change. This substitution occurs in a highly hydrophobic portion of the protein that is thought to be an alpha-helical transmembrane segment. The presence of a helix-breaking amino acid such as proline in this segment is likely to influence the ability of the protein to interact with the membrane.
在动物和人类中发生的几种遗传性疾病会导致无法合成正常的髓磷脂。其中一些疾病以X连锁的方式遗传。髓磷脂蛋白脂蛋白（PLP）基因定位于X染色体，这使得对X连锁髓鞘形成障碍的研究转向了PLP。髓磷脂缺陷大鼠就是这样一种X连锁脱髓鞘突变体。从由髓磷脂缺陷大鼠脑mRNA构建的cDNA文库中，我们分离并测序了与PLP及其可变剪接异构体DM-20相对应的cDNA。在这些cDNA中检测到一个A到C的转换，这导致PLP和DM-20中第74位氨基酸处的苏氨酸变为脯氨酸。在cDNA序列中未发现其他替换。使用聚合酶链反应扩增和相应基因组区域的测序来确认单碱基变化。这种替换发生在蛋白质的一个高度疏水部分，该部分被认为是一个α螺旋跨膜片段。在该片段中存在脯氨酸这样的破坏螺旋的氨基酸可能会影响蛋白质与膜相互作用的能力。
