Primary structure of dystrophin-related protein
Primary structure of dystrophin-related protein
复制标题
抗肌萎缩蛋白相关蛋白的一级结构
作者：
J. Tinsley;D. Blake;A. Roche;U. Fairbrother;J. Riss;B. Byth;A. Knight;J. Kendrick;G. Suthers;D. Love;Y. Edwards;K. Davies
肌营养不良相关蛋白（DRP或'utrophin' 1）主要位于正常成人肌肉的神经肌肉接头2 -4。在杜氏肌营养不良症（DMD）患者中缺乏肌营养不良蛋白的情况下，DRP也存在于肌膜中3 -7。DRP在胎儿和再生肌肉中表达，并且可能在早期发育中发挥与肌营养不良蛋白类似的作用3，7-9，尽管还有待确定DRP是否可以在成人组织中功能性地替代肌营养不良蛋白。以前，我们描述了一个3.5-脱氢酶互补DNA克隆，表现出80%的同源性的C-末端结构域的抗肌萎缩蛋白10。该序列鉴定了定位于人类6号染色体的13-腺苷酸酶转录物（参考文献2，11）。针对基因产物产生的抗体在所有检查的组织中鉴定出相对分子质量约为400 K的多肽7，8，12。为了更详细地研究DRP和dystrophin之间的关系，我们克隆了整个DRP cDNA并进行了序列测定。DRP和抗肌萎缩蛋白之间的同源性延伸到它们的整个长度，表明它们来自共同的祖先基因。一级序列的比较分析突出了功能重要性区域，包括可能介导肌细胞中DRP和肌营养不良蛋白定位的区域。
DYSTROPHIN-RELATED protein (DRP or 'utrophin'1) is localized in normal adult muscle primarily at the neuromuscular junction2–4. In the absence of dystrophin in Duchenne muscular dystrophy (DMD) patients, DRP is also present in the sarcolemma3–7. DRP is expressed in fetal and regenerating muscle and may play a similar role to dystrophin in early development3,7–9, although it remains to be determined whether DRP can functionally replace dystrophin in adult tissue. Previously we described a 3.5-kilobase complementary DNA clone that exhibits 80 per cent homology to the C-terminal domain of dystrophin10. This sequence identifies a 13-kilobase transcript that maps to human chromosome 6 (refs 2, 11). Antibodies raised against the gene product identify a polypeptide with a relative molecular mass of about 400K in all tissues examined7,8,12. To investigate the relationship between DRP and dystrophin in more detail, we have cloned and sequenced the whole DRP cDNA. Homology between DRP and dystrophin extends over their entire length, suggesting that they derive from a common ancestral gene. Comparative analysis of primary sequences highlights regions of functional importance, including those that may mediate the localization of DRP and dystrophin in the muscle cell.