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.
Keyphrases
- molecular dynamics simulations
- endoplasmic reticulum stress
- cell death
- oxidative stress
- magnetic resonance
- single molecule
- cell cycle arrest
- crystal structure
- living cells
- binding protein
- signaling pathway
- endoplasmic reticulum
- sensitive detection
- cell proliferation
- quantum dots
- wastewater treatment
- antibiotic resistance genes
- pi k akt
- visible light