Tsuda M, Kaneda M, Sakiyama T, Inana I, Owada M, Kiryu C, Shiraishi T, Kakinuma K
Department of Pediatrics, Nihon University School of Medicine, Tokyo, Japan.
Hum Genet. 1998 Oct;103(4):377-81. doi: 10.1007/s004390050836.
A membrane-bound cytochrome b558, a heterodimer consisting of gp91-phox and p22-phox, is a critical component of the superoxide (O2-)-generating reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in phagocytes. Chronic granulomatous disease (CGD) is characterized by recurrent bacterial infection caused by a defect of the oxidase. Both subunits are absent from phagocytes in typical X-linked recessive CGD patients who are primarily defective in gp91-phox. We report here an atypical case of X-linked CGD in which neutrophils showed a complete absence of O2--forming NADPH oxidase activity, but a small amount (about 10% of control) of both subunits was detected by immunoblot analysis. Spectrophotometric studies of the neutrophils with a recently developed sensitive method gave no evidence for the heme spectrum in the cytochrome b558, of this CGD. Reverse transcription/polymerase chain reaction and sequence analysis revealed a C to T transition replacing histidine at amino acid position 101 (His101) by tyrosine in gp91-phox. These results provide evidence that His101 of gp91-phox is the one of the heme-binding ligands of cytochrome b558.
膜结合细胞色素b558是一种由gp91 - phox和p22 - phox组成的异二聚体，是吞噬细胞中产生超氧化物（O2-）的还原型烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶的关键成分。慢性肉芽肿病（CGD）的特征是由氧化酶缺陷引起的反复细菌感染。在典型的X连锁隐性CGD患者中，吞噬细胞中这两个亚基均缺失，这些患者主要存在gp91 - phox缺陷。我们在此报告一例非典型X连锁CGD病例，其中中性粒细胞完全缺乏形成O2-的NADPH氧化酶活性，但通过免疫印迹分析检测到少量（约为对照的10%）的两个亚基。用最近开发的一种灵敏方法对中性粒细胞进行分光光度研究，未发现该CGD患者细胞色素b558中有血红素光谱的证据。逆转录/聚合酶链反应和序列分析显示，gp91 - phox中第101位氨基酸（His101）处的组氨酸被酪氨酸取代，发生了C到T的转换。这些结果证明，gp91 - phox的His101是细胞色素b558的血红素结合配体之一。
