Mutation eliminating mitochondrial leader sequence of methylmalonyl-CoA mutase causes muto methylmalonic acidemia.
Mutation eliminating mitochondrial leader sequence of methylmalonyl-CoA mutase causes muto methylmalonic acidemia.
复制标题
消除甲基丙二酰辅酶A变位酶线粒体前导序列的突变会导致突变甲基丙二酸血症。
DOI：
10.1073/pnas.87.8.3147
复制
发表时间：
1990
影响因子：
11.1
通讯作者：
Rosenberg,LE
中科院分区：
文献类型：
--
作者：
Ledley,FD;Jansen,R;Nham,SU;Fenton,WA;Rosenberg,LE
甲基丙二酸辅酶A变位酶（EC 5.4.99.2）是一种线粒体基质酶，其活性在遗传性疾病甲基丙二酸血症中缺乏。以前对甲基丙二酸血症患者的原代成纤维细胞系的研究已经描述了这种疾病的各种生化表型。一个细胞系与原发性β-apoenzyme缺乏症表现出一个特别不寻常的表型，它表达了一个异常小，不稳定的免疫反应蛋白，这是不是进口的线粒体。我们现在报告的cDNA编码这种突变蛋白的克隆和测序。突变是一个单碱基的变化，胞嘧啶-胸腺嘧啶转换，在线粒体前导序列的17位引入了一个琥珀终止密码子。由这些细胞产生的免疫反应性蛋白反映了该终止密码子下游的AUG密码子的翻译，因此缺乏线粒体前导肽。这种突变代表了一类突变的复杂原型，其中线粒体靶向序列的缺失导致功能基因产物的缺失。
Methylmalonyl-CoA mutase (EC 5.4.99.2) is a mitochondrial matrix enzyme whose activity is deficient in the inherited disorder methylmalonic acidemia. Previous studies on primary fibroblast cell lines from patients with methylmalonic acidemia have delineated a variety of biochemical phenotypes underlying this disorder. One cell line with primary mutase apoenzyme deficiency exhibited a particularly unusual phenotype; it expressed an abnormally small and unstable immunoreactive protein, which was not imported by mitochondria. We now report cloning and sequencing of the cDNA encoding this mutant protein. The mutation is a single base change, a cytosine----thymine transition, which introduces an amber termination codon at position 17 within the mitochondrial leader sequence. The immunoreactive protein produced by these cells reflects translation from AUG codons downstream from this termination codon and, hence, lacks a mitochondrial leader peptide. This mutation represents a complex prototype for a class of mutations in which absence of the mitochondrial targeting sequence leads to absence of a functioning gene product.