细胞色素<i>c的</i>替代构象：结构，功能和检测,Biochemistry

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细胞色素c的替代构象：结构，功能和检测
Biochemistry ( IF 2.9 ) Pub Date : 2016-01-15 00:00:00 , DOI: 10.1021/acs.biochem.5b01385
Luciana Hannibal _{1,

2,

3} , Florencia Tomasina _{1,

2} , Daiana A. Capdevila ₄ , Verónica Demicheli _{1,

2} , Verónica Tórtora _{1,

2} , Damián Alvarez-Paggi ₄ , Ronald Jemmerson ₅ , Daniel H. Murgida ₄ , Rafael Radi _{1,

2}

Affiliation

细胞色素c（cyt c）是约100个氨基酸残基的阳离子血红蛋白，具有出色的功能通用性。cyt c的主要功能是电子在呼吸链中的转移，但它也被认为是内在凋亡途径，线粒体氧化蛋白折叠机制的关键组成部分，并据推测是胞质溶胶中的氧化还原传感器，以及其他已报道的功能。人们认为，向其他构象的过渡和过氧化物酶活性的获得，可以进一步实现cyt c的多种功能及其跨细胞区室的转运。cyt c在体外的直接相互作用对于心磷脂，翻译后修饰（例如酪氨酸硝化，磷酸化，蛋氨酸亚砜氧化，突变，甚至电场的细微变化）会导致多种构象状态，这些构象状态可能与生物学相关。这些替代构象的鉴定及其在体内功能的阐明仍然是主要的挑战。在这里，我们统一了支持功能性月光的cyt c的结构灵活性的认识，并回顾了生化和免疫化学证据，证实cyt c在正常和改变的细胞体内平衡过程中发生构象变化。

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Alternative Conformations of Cytochrome c: Structure, Function, and Detection

Cytochrome c (cyt c) is a cationic hemoprotein of ∼100 amino acid residues that exhibits exceptional functional versatility. While its primary function is electron transfer in the respiratory chain, cyt c is also recognized as a key component of the intrinsic apoptotic pathway, the mitochondrial oxidative protein folding machinery, and presumably as a redox sensor in the cytosol, along with other reported functions. Transition to alternative conformations and gain-of-peroxidase activity are thought to further enable the multiple functions of cyt c and its translocation across cellular compartments. In vitro, direct interactions of cyt c with cardiolipin, post-translational modifications such as tyrosine nitration, phosphorylation, methionine sulfoxidation, mutations, and even fine changes in electrical fields lead to a variety of conformational states that may be of biological relevance. The identification of these alternative conformations and the elucidation of their functions in vivo continue to be a major challenge. Here, we unify the knowledge of the structural flexibility of cyt c that supports functional moonlighting and review biochemical and immunochemical evidence confirming that cyt c undergoes conformational changes during normal and altered cellular homeostasis.

更新日期：2016-01-15

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