Understanding the structure-function relationship of Cytochrome c probing its conformational states
Chemistry Department "Ugo Schiff"
Università di Firenze
Cytochrome c (Cyt c) is a single polypeptide chain hemoprotein located in the mitochodrial intermembrane space, acting as an electron carrier in the respiratory chain . Moreover, direct interaction with a phospholipid of the mitochondrial membrane, cardiolipin [CL], induces acquisition of peroxidase activity and subsequent release of Cyt c into the cytosol, where it acts as an apoptosis initiator . Under physiological conditions, His18 and Met80 are the fifth and sixth axial ligands, respectively, of the heme iron Cyt c, but extensive studies on protein folding have showed that the Met80 sixth ligand can be replaced by other internal or exogenous ligands depending on the pH or the presence of denaturing agents . Spectroscopy has played an important role to disclose the nature of the substituting ligand in the nonnative states. Among the various techniques, resonance Raman (RR) spectroscopy has been extensively applied. In particular, specific RR markers have been identified for each non-native ligand .
The seminar is focused on the identification of the RR markers of the various nonnative misfolded forms and on the very recent results providing new insight into the interaction of Cyt c with CL  and the effect of mutating key residues in the human Cyt c heme cavity [6,7]. These studies are of particular importance since, based on the identification of the nonnative species, they provide important information on the structure-function relationship.
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