Folding studies of Cox17 reveal an important interplay of cysteine oxidation and copper binding
Folding studies of Cox17 reveal an important interplay of cysteine oxidation and copper binding
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DOI：
10.1016/j.str.2005.02.015
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发表时间：
2005-05-01
期刊：
影响因子：
5.7
通讯作者：
Winge, DR
中科院分区：
文献类型：
--
作者：
Arnesano, F;Balatri, E;Winge, DR
Cox 17是参与细胞色素c氧化酶（考克斯）组装的关键线粒体铜分子伴侣。氧化的apoCox 17同种型的NMR溶液结构由卷曲螺旋构象组成，该卷曲螺旋构象由涉及Cys（26）/Cys（57）和Cys（36）/Cys（47）的两个二硫键稳定。这似乎是一类蛋白质的保守三级折叠，位于线粒体膜间隙内，含有双Cys-x（9）-Cys序列基序。在Cu（I）结合形成Cu（1）Cox 17复合物之前，需要将一个二硫键从Cys（26）/Cys（57）异构化为Cys（24）/Cys（57）。在脱辅基蛋白的进一步氧化后，获得具有三个二硫键的形式。所有二硫键的还原提供了一种熔融的球状物形式，其可以转化为能够在聚铜簇中结合多达四个Cu（I）离子的额外构象异构体。这种形式的蛋白质是寡聚的。这些属性的框架内的线粒体进口和考克斯大会的完整模型。
Cox17 is a key mitochondrial copper chaperone involved in the assembly of cytochrome c oxidase (COX). The NMR solution structure of the oxidized apoCox17 isoform consists of a coiled-coil conformation stabilized by two disulfide bonds involving Cys(26)/Cys(57) and Cys(36)/Cys(47). This appears to be a conserved tertiary fold of a class of proteins, localized within the mitochondrial intermembrane space, that contain a twin Cys-x(9)-Cys sequence motif. An isomerization of one disulfide bond from Cys(26)/Cys(57) to Cys(24)/Cys(57) is required prior to Cu(I) binding to form the Cu(1)Cox17 complex. Upon further oxidation of the apo-protein, a form with three disulfide bonds is obtained. The reduction of all disulfide bonds provides a molten globule form that can convert to an additional conformer capable of binding up to four Cu(I) ions in a polycopper cluster. This form of the protein is oligomeric. These properties are framed within a complete model of mitochondrial import and COX assembly.