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

• Published in: Life (Basel, Switzerland) Switzerland), 2021-09, Vol.11 (10), p.1031
• Main Authors: Zhan, Jianhua, Zhang, Guangqing, Chai, Xin, Zhu, Qinjun, Sun, Peng, Jiang, Bin, Zhou, Xin, Zhang, Xu, Liu, Maili
• Format: Article
• Language: English
• Subjects: Apoptosis; Binding sites; Cardiolipin; conformation; Coordination; Cytochrome; Cytochrome c; Cytochromes; Cytoplasm; Diphosphatidylglycerol; Experiments; Heme; Magnetic resonance spectroscopy; Mass spectrometry; methyl; Mitochondria; Mutation; NMR; NMR spectroscopy; Nuclear magnetic resonance; Peroxidase; Proteins; Scientific imaging; Yeasts
• ISSN: 2075-1729; 2075-1729
• 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.