Zhan Jianhua, Zhang Guangqing, Chai Xin, Zhu Qinjun, Sun Peng, Jiang Bin, Zhou Xin, Zhang Xu, Liu Maili
Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement of Science and Technology, Chinese Academy of Sciences, Wuhan 430071, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Life (Basel). 2021 Sep 30;11(10):1031. doi: 10.3390/life11101031.
Conformational change of cytochrome c (cyt c) caused by interaction with cardiolipin (CL) is an important step during apoptosis, but the underlying mechanism is controversial. To comprehensively clarify the structural transformations of cyt c upon interaction with CL and avoid the unpredictable alias that might come from protein labeling or mutations, the conformation of purified yeast iso-1 cyt c with natural isotopic abundance in different contents of CL was measured by using NMR spectroscopy, in which the trimethylated group of the protein was used as a natural probe. The data demonstrate that cyt c has two partially unfolded conformations when interacted with CL: one with Fe-His33 coordination and the other with a penta-coordination heme. The Fe-His33 coordination conformation can be converted into a penta-coordination heme conformation in high content of CL. The structure of cyt c becomes partially unfolded with more exposed heme upon interaction with CL, suggesting that cyt c prefers a high peroxidase activity state in the mitochondria, which, in turn, makes CL easy to be oxidized, and causes the release of cyt c into the cytoplasm as a trigger in apoptosis.
细胞色素c（cyt c）与心磷脂（CL）相互作用引起的构象变化是细胞凋亡过程中的一个重要步骤，但其潜在机制仍存在争议。为了全面阐明cyt c与CL相互作用时的结构转变，并避免蛋白质标记或突变可能带来的不可预测的别名，利用核磁共振光谱法测定了在不同CL含量下具有天然同位素丰度的纯化酵母同工酶-1 cyt c的构象，其中蛋白质的三甲基化基团用作天然探针。数据表明，cyt c与CL相互作用时具有两种部分展开的构象：一种是Fe-His33配位，另一种是五配位血红素。在高含量CL中，Fe-His33配位构象可转化为五配位血红素构象。cyt c与CL相互作用时，其结构变得部分展开，血红素暴露更多，这表明cyt c在线粒体中倾向于高过氧化物酶活性状态，这反过来又使CL易于被氧化，并导致cyt c作为细胞凋亡的触发因素释放到细胞质中。
