Mitochondrial thiol oxidase Erv1: both shuttle cysteine residues are required for its function with distinct roles.
Mitochondrial thiol oxidase Erv1: both shuttle cysteine residues are required for its function with distinct roles.
复制标题
线粒体硫醇氧化酶ERV1：两种穿梭半胱氨酸残基都具有不同作用的功能。
DOI：
10.1042/bj20131540
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发表时间：
2014-06-01
期刊：
影响因子：
--
通讯作者：
Lu H
中科院分区：
文献类型：
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作者：
Ang SK;Zhang M;Lodi T;Lu H
ERV1（对于呼吸和生存能力1）是MIA的重要组成部分（线粒体导入和组装），在线粒体间膜间空间蛋白的氧化折叠中起重要作用氧化硫醇又通过其N末端重新氧化MIA40 Cys30 – Cys33二硫化物，尚不清楚从MIA40 CPC主题中的ERV1中继电子中的两个穿梭的半胱氨酸如何使用酵母遗传的cyertle cyltle cyltle cyern cyern conserel，cys130 cys130 – cys130 cys130 – cys133 tle半胱氨酸的保留确实是进口MIA途径底物和ERV1酶功能向氧化物MIA40进发，我们的结果表明，ERV1的两个穿梭的半胱氨酸保留在功能上是不同的。 MIA40 CPC主题；（II）解决ERV1 Cys33 – Cys130中间二硫化物，我们包括两个穿梭的半胱氨酸固定剂是ERV1功能所必需的，并扮演互补但独特的角色以确保快速的活性ERV1。
ERV1是一种氧化磺胺，这是线粒体MIA途径的必不可少的成分。
Erv1 (essential for respiration and viability 1), is an essential component of the MIA (mitochondrial import and assembly) pathway, playing an important role in the oxidative folding of mitochondrial intermembrane space proteins. In the MIA pathway, Mia40, a thiol oxidoreductase with a CPC motif at its active site, oxidizes newly imported substrate proteins. Erv1 a FAD-dependent thiol oxidase, in turn reoxidizes Mia40 via its N-terminal Cys30–Cys33 shuttle disulfide. However, it is unclear how the two shuttle cysteine residues of Erv1 relay electrons from the Mia40 CPC motif to the Erv1 active-site Cys130–Cys133 disulfide. In the present study, using yeast genetic approaches we showed that both shuttle cysteine residues of Erv1 are required for cell growth. In organelle and in vitro studies confirmed that both shuttle cysteine residues were indeed required for import of MIA pathway substrates and Erv1 enzyme function to oxidize Mia40. Furthermore, our results revealed that the two shuttle cysteine residues of Erv1 are functionally distinct. Although Cys33 is essential for forming the intermediate disulfide Cys33–Cys130′ and transferring electrons to the redox active-site directly, Cys30 plays two important roles: (i) dominantly interacts and receives electrons from the Mia40 CPC motif; and (ii) resolves the Erv1 Cys33–Cys130 intermediate disulfide. Taken together, we conclude that both shuttle cysteine residues are required for Erv1 function, and play complementary, but distinct, roles to ensure rapid turnover of active Erv1. Erv1 is a sulfydryl oxidase, an essential component of mitochondrial MIA pathway. The present study shows that both shuttle cysteine residues of Erv1 are required for its function, they play complementary, but distinct, roles to ensure rapid turnover of active enzyme.