Structural Characteristics of Stable Folding Intermediates of Yeast Iso-1-Cytochrome-c

Cytochrome-c (cyt-c) is an electron transport protein, and it is present throughout the evolution. More than 280 sequences have been reported in the protein sequence database (www.uniprot.org). Though sequentially diverse, cyt-c has essentially retained its tertiary structure or fold. Thus a vast data set of varied sequences with retention of similar structure and function makes it a primary candidate for studying molecular evolution, phylogenetics and sequence conservation. When amino acid sequences of mammalian cyts-c are aligned with the sequence of the yeast iso-1-cyt-c (y-cyt-c), it is observed that the yeast protein not only contains five extra N-terminal residues but it has only 60% sequence homology, e.g., with the horse heart cyt-c. Structural and thermodynamic studies suggest that there are four states in the folding equation of y-cyt-c, i.e., Denatured (D) state ↔ Pre molten globule (PMG) state ↔ Molten Globule (MG) state ↔ N (Native) state. This review summarises findings of structural and thermodynamic characteristics of these thermodynamic states of y-cyt-c and its folding mechanism.