A Conformational Switch to β-Sheet Structure in Cytochrome c Leads to Heme Exposure. Implications for Cardiolipin Peroxidation and Apoptosis

Abstract

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.