Becoming a peroxidase: cardiolipin-induced unfolding of cytochrome c.
Becoming a peroxidase: cardiolipin-induced unfolding of cytochrome c.
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成为过氧化物酶：Cardiolipin诱导的细胞色素c的展开。
DOI：
10.1021/jp402104r
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发表时间：
2013-10-24
期刊：
影响因子：
--
通讯作者：
Pletneva EV
中科院分区：
文献类型：
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作者：
Muenzner J;Toffey JR;Hong Y;Pletneva EV
细胞色素c（cyt c）与一种独特的线粒体甘油磷脂心磷脂（CL）的相互作用与该蛋白在氧化磷酸化和细胞凋亡中的功能有关。结合到含CL的膜促进细胞色素c展开，并显着增强蛋白质的过氧化物酶活性，这在细胞凋亡的早期阶段是至关重要的。我们已经采用了一个收集的7个丹磺酰变异的马心细胞色素c，以探测在此功能转换的步骤的顺序。动力学测量已解开CL诱导的细胞色素C展开过程中的四个不同的过程：快速蛋白质结合CL脂质体;重排的蛋白质亚结构与小展开能量;部分插入到脂质双层的蛋白质;和广泛的蛋白质重组导致“开放”的扩展结构。虽然早期的重排依赖于天然结构中的折叠子层次结构，但后期的大规模展开过程受到蛋白质与膜表面相互作用的影响。细胞色素C结构的开放暴露血红素基团，这增强了蛋白质的过氧化物酶活性，并且还释放了C-末端螺旋以帮助蛋白质通过CL膜的易位。
Interactions of cytochrome c (cyt c) with a unique mitochondrial glycerophospholipid cardiolipin (CL) are relevant for the protein’s function in oxidative phosphorylation and apoptosis. Binding to CL-containing membranes promotes cyt c unfolding and dramatically enhances the protein’s peroxidase activity, which is critical in early stages of apoptosis. We have employed a collection of seven dansyl variants of horse heart cyt c to probe the sequence of steps in this functional transformation. Kinetic measurements have unraveled four distinct processes during CL-induced cyt c unfolding: rapid protein binding to CL liposomes; rearrangements of protein substructures with small unfolding energies; partial insertion of the protein into the lipid bilayer; and extensive protein restructuring leading to “open” extended structures. While early rearrangements depend on a hierarchy of foldons in the native structure, the later process of large-scale unfolding is influenced by protein interactions with the membrane surface. The opening of the cyt c structure exposes the heme group, which enhances the protein’s peroxidase activity and also frees the C-terminal helix to aid in the translocation of the protein through CL membranes.