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

Cytochromec (cytc) 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, cytc 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 cytsc are aligned with the sequence of the yeast iso1cytc (ycytc), it is observed that the yeast protein not only contains five extra Nterminal residues but it has only 60% sequence homology, e.g., with the horse heart cytc. Structural and thermodynamic studies suggest that there are four states in the folding equation of ycytc, 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 ycytc and its folding mechanism.