Dimerization-induced conformational transitions of yeast iso-1 cytochrome c

Cytochrome c is a multifunctional protein involved in electron transport and apoptosis. However, its conformational landscape is complex and heterogeneous, which has obscured the functional understanding-particularly regarding its long-observed dimerized state. In this study, we characterized the conformational distributions of yeast iso-1 cytochrome c (ycyt c) by exploiting the native trimethylated K72 residue (K72me3) as an NMR molecular probe. Our analysis revealed that C102-mediated dimerization disrupts the M80-heme iron coordination, shifting the equilibrium toward conformations featuring an exposed heme and enhanced peroxidase activity. Furthermore, molecular dynamics simulations suggest that the oxidized monomer samples an "open" conformation, which increases the active site accessibility, likely contributing to its elevated peroxidase activity. These findings shed light on the biological significance of C102 in ycyt c and propose a novel mechanism by which dimerization activates the protein as a peroxidase, potentially protecting cells against apoptosis or other oxidative damages.