Ferricytochrome is a flexible heme protein known to partially unfold at a pH above 8, generally reversibly. This study reveals the unexpected conformational change that ferricytochrome c undergoes after exposing it to pH 11.5 for a week. A partially unfolded state was formed which is in equilibrium with an aggregated, non-soluble state at pH 6-8 and with soluble aggregates at pH 9. UVCD data indicate that the secondary structure remains mostly intact. The heme is hexacoordinated low spin (pH >6), likely with two axial histidines. A new conformation with iron in a quantum mixed spin state becomes populated below pH 6. Our data indicate the population of a frustrated misfolded state, occupied as a result of a folding pathway determined by our experiment, for which the glass transition temperature is higher than the folding temperature. We speculate that cytochrome c might adopt a similar state on the surface of liposomes.

Population of a misfolded state of cytochrome C at native conditions

244th National Meeting (2012)

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