A conformational switch to β-sheet structure in cytochrome c leads to heme exposure. Implications for cardiolipin peroxidation and apoptosis

Ultraviolet resonance Raman spectroscopy reveals that, when heated at pH 3, a substantial fraction (30%) of cytochrome c converts to a β-sheet structure, at the expense of turns and helices. β-sheet formation is rapid, exhibiting a 2 μs rise time, following a temperature jump. It is proposed that a short β-sheet segment, comprising residues 37-39 and 58-61, extends itself into the large 37-61 loop when the latter is destabilized by protonation of H26, which forms an anchoring H-bond to loop residue P44. This conformation change ruptures the Met80-Fe bond, as revealed by changes in ligation-sensitive heme-resonant Raman bands. It also induces peroxidase activity with the same temperature profile. This process is suggested to model the apoptotic peroxidation of cardiolipin by cytochrome c.