NMR Reveals the Conformational Changes of Cytochrome C upon Interaction with Cardiolipin.

NMR Reveals the Conformational Changes of Cytochrome C upon Interaction with Cardiolipin.
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NMR 显示细胞色素 C 与心磷脂相互作用时的构象变化。

DOI:
10.3390/life11101031
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发表时间:
2021-09-30
期刊:
Life (Basel, Switzerland)
影响因子:
--
通讯作者:
Liu M
Liu M
中科院分区:
其他
文献类型:
--
作者:
Zhan J;Zhang G;Chai X;Zhu Q;Sun P;Jiang B;Zhou X;Zhang X;Liu M

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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,但其机制仍存在争议。为了全面阐明Cyt c与CL相互作用后的结构变化,避免蛋白质标记或突变可能导致的不可预测的别名,采用核磁共振技术,以蛋白质的三甲基化基团为天然探针,测定了不同CL含量下具有天然同位素丰度的纯化酵母iso-1 cyt c的构象.数据表明,细胞色素c有两个部分未折叠的构象时,与CL相互作用:一个与Fe-His 33协调和其他与五配位血红素。当CL含量较高时,Fe-His 33配位构象转变为五配位血红素构象。与CL相互作用后,cyt c的结构变得部分展开,更多暴露的血红素,表明cyt c喜欢线粒体中的高过氧化物酶活性状态,这反过来又使CL容易被氧化,并导致cyt c释放到细胞质中作为凋亡的触发器。
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.
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