Muenzner Julia, Pletneva Ekaterina V
Department of Chemistry, Dartmouth College, Hanover, NH 03755, United States.
Department of Chemistry, Dartmouth College, Hanover, NH 03755, United States.
Chem Phys Lipids. 2014 Apr;179:57-63. doi: 10.1016/j.chemphyslip.2013.11.002. Epub 2013 Nov 16.
Interactions of cytochrome c (cyt c) with cardiolipin (CL) play a critical role in early stages of apoptosis. Upon binding to CL, cyt c undergoes changes in secondary and tertiary structure that lead to a dramatic increase in its peroxidase activity. Insertion of the protein into membranes, insertion of CL acyl chains into the protein interior, and extensive unfolding of cyt c after adsorption to the membrane have been proposed as possible modes for interaction of cyt c with CL. Dissociation of Met80 is accompanied by opening of the heme crevice and binding of another heme ligand. Fluorescence studies have revealed conformational heterogeneity of the lipid-bound protein ensemble with distinct polypeptide conformations that vary in the degree of protein unfolding. We correlate these recent findings to other biophysical observations and rationalize the role of experimental conditions in defining conformational properties and peroxidase activity of the cyt c ensemble. Latest time-resolved studies propose the trigger and the sequence of cardiolipin-induced structural transitions of cyt c.
细胞色素c（cyt c）与心磷脂（CL）的相互作用在细胞凋亡的早期阶段起着关键作用。与CL结合后，cyt c的二级和三级结构发生变化，导致其过氧化物酶活性显著增加。蛋白质插入膜中、CL酰基链插入蛋白质内部以及cyt c吸附到膜后广泛展开，被认为是cyt c与CL相互作用的可能模式。Met80的解离伴随着血红素裂隙的打开和另一种血红素配体的结合。荧光研究揭示了脂质结合蛋白集合体的构象异质性，其具有不同的多肽构象，蛋白质展开程度各不相同。我们将这些最新发现与其他生物物理观察结果相关联，并合理化了实验条件在定义cyt c集合体的构象性质和过氧化物酶活性中的作用。最新的时间分辨研究提出了心磷脂诱导的cyt c结构转变的触发因素和序列。
