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首页> 外文期刊>Biochimica et biophysica acta. Molecular basis of disease: BBA >Molecular quality control machinery contributes to the leukocyte NADPH oxidase deficiency in chronic granulomatous disease
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Molecular quality control machinery contributes to the leukocyte NADPH oxidase deficiency in chronic granulomatous disease

机译：分子质量控制机制导致慢性肉芽肿病中白细胞NADPH氧化酶缺乏

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摘要

Chronic granulomatous disease (CGD) is an inherited immunodeficiency disease caused by defects in leukocyte NADPH oxidase. Various inherited defects in one of the membrane-bound components of NADPH oxidase, gp91-phox, cause X-linked (X91) CGD. Analysis of three patients with X91 CGD revealed that different mechanisms of molecular quality control lead to the common phenotype of absence of mature membrane-bound NADPH oxidase complex in leukocytes. In the first patient, aberrant intron splicing created a premature stop codon. However, the mutant mRNA was degraded prematurely, which prevented the production of truncated protein. In the second patient, a frameshift mutation with the potential to generate a gp91-phox polypeptide, with an aberrant and elongated C-terminus, led to barely detectable levels of gp91-phox, even though the reported functional domains of the protein appeared unaffected. In the third patient, a point mutation created a single amino acid change in the predicted FAD-binding site of gp91-phox. Although gp91-phox was detectable with Western blotting, no cytochrome b_(558) was expressed on the cell surface. These analyses showed that molecular quality control machinery plays an important role in the pathogenesis of CGD, not only in the X91~0 but also in the X91~- form of this X-linked disease.
机译：慢性肉芽肿性疾病（CGD）是由白细胞NADPH氧化酶缺陷引起的遗传性免疫缺陷疾病。 NADPH氧化酶的膜结合成分之一中的各种遗传缺陷gp91-phox导致X连锁（X91）CGD。对三名X91 CGD患者的分析表明，分子质量控制的不同机制导致白细胞中缺乏成熟的膜结合NADPH氧化酶复合物的常见表型。在第一例患者中，异常的内含子剪接产生了过早的终止密码子。但是，突变mRNA过早降解，这阻止了截短蛋白的产生。在第二例患者中，尽管报道的蛋白质功能域似乎不受影响，但具有产生gp91-phox多肽，具有异常和延长的C末端的潜力的移码突变导致gp91-phox的水平几乎无法检测到。在第三位患者中，点突变在gp91-phox的预测FAD结合位点产生了单个氨基酸变化。尽管可以通过蛋白质印迹法检测到gp91-phox，但是在细胞表面没有表达细胞色素b_（558）。这些分析表明，分子质量控制机制在CGD的发病机理中起着重要作用，不仅在这种X连锁疾病的X91〜0中，而且在X91〜-形式中也是如此。

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