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人类Cox17的结构动力学特征

A structural-dynamical characterization of human Cox17.

作者信息

Banci Lucia, Bertini Ivano, Ciofi-Baffoni Simone, Janicka Anna, Martinelli Manuele, Kozlowski Henryk, Palumaa Peep

机构信息

Magnetic Resonance Center Centro Risonanze Magnetiche (CERM) and Department of Chemistry, University of Florence, Via Luigi Sacconi 6, 50019, Sesto Fiorentino, Florence, Italy.

出版信息

J Biol Chem. 2008 Mar 21;283(12):7912-20. doi: 10.1074/jbc.M708016200. Epub 2007 Dec 19.

Abstract

Human Cox17 is a key mitochondrial copper chaperone responsible for supplying copper ions, through the assistance of Sco1, Sco2, and Cox11, to cytochrome c oxidase, the terminal enzyme of the mitochondrial energy transducing respiratory chain. A structural and dynamical characterization of human Cox17 in its various functional metallated and redox states is presented here. The NMR solution structure of the partially oxidized Cox17 (Cox17(2S-S)) consists of a coiled coil-helix-coiled coil-helix domain stabilized by two disulfide bonds involving Cys(25)-Cys(54) and Cys(35)-Cys(44), preceded by a flexible and completely unstructured N-terminal tail. In human Cu(I)Cox17(2S-S) the copper(I) ion is coordinated by the sulfurs of Cys(22) and Cys(23), and this is the first example of a Cys-Cys binding motif in copper proteins. Copper(I) binding as well as the formation of a third disulfide involving Cys(22) and Cys(23) cause structural and dynamical changes only restricted to the metal-binding region. Redox properties of the disulfides of human Cox17, here investigated, strongly support the current hypothesis that the unstructured fully reduced Cox17 protein is present in the cytoplasm and enters the intermembrane space (IMS) where is then oxidized by Mia40 to Cox17(2S-S), thus becoming partially structured and trapped into the IMS. Cox17(2S-S) is the functional species in the IMS, it can bind only one copper(I) ion and is then ready to enter the pathway of copper delivery to cytochrome c oxidase. The copper(I) form of Cox17(2S-S) has features specific for copper chaperones.

摘要

人类Cox17是一种关键的线粒体铜伴侣蛋白,负责通过Sco1、Sco2和Cox11的协助,将铜离子供应给细胞色素c氧化酶,即线粒体能量转换呼吸链的末端酶。本文介绍了人类Cox17在其各种功能金属化和氧化还原状态下的结构和动力学特征。部分氧化的Cox17(Cox17(2S-S))的核磁共振溶液结构由一个卷曲螺旋-螺旋-卷曲螺旋-螺旋结构域组成,该结构域由涉及Cys(25)-Cys(54)和Cys(35)-Cys(44)的两个二硫键稳定,前面是一个灵活且完全无结构的N端尾巴。在人类Cu(I)Cox17(2S-S)中,铜(I)离子由Cys(22)和Cys(23)的硫原子配位,这是铜蛋白中Cys-Cys结合基序的第一个例子。铜(I)的结合以及涉及Cys(22)和Cys(23)的第三个二硫键的形成仅导致局限于金属结合区域的结构和动力学变化。本文研究的人类Cox17二硫键的氧化还原特性有力地支持了当前的假设,即无结构的完全还原的Cox17蛋白存在于细胞质中,并进入膜间隙(IMS),然后在那里被Mia40氧化为Cox17(2S-S),从而变得部分结构化并被困在IMS中。Cox17(2S-S)是IMS中的功能形式,它只能结合一个铜(I)离子,然后准备进入将铜输送到细胞色素c氧化酶的途径。Cox17(2S-S)的铜(I)形式具有铜伴侣蛋白特有的特征。

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