Phosphorylation disrupts long-distance electron transport in cytochrome c
Alexandre M. J. Gomila, Gonzalo Pérez‐Mejías, Alba Nin‐Hill, Alejandra Guerra‐Castellano, Laura Casas-Ferrer, Sthefany Ortiz-Tescari, Antonio Dı́az-Quintana, Josep Samitier, Carme Rovira, Miguel Á. De la Rosa, Irene Díaz‐Moreno, Pau Gorostiza, Marina I. Giannotti, Anna Lagunas
Abstract
Abstract It has been recently shown that electron transfer between mitochondrial cytochrome c and the cytochrome c 1 subunit of the cytochrome bc 1 can proceed at long-distance through the aqueous solution. Cytochrome c is thought to adjust its activity by changing the affinity for its partners via Tyr48 phosphorylation, but it is unknown how it impacts the nanoscopic environment, interaction forces, and long-range electron transfer. Here, we constrain the orientation and separation between cytochrome c 1 and cytochrome c or the phosphomimetic Y48 p CMF cytochrome c , and deploy an array of single-molecule, bulk, and computational methods to investigate the molecular mechanism of electron transfer regulation by cytochrome c phosphorylation. We demonstrate that phosphorylation impairs long-range electron transfer, shortens the long-distance charge conduit between the partners, strengthens their interaction, and departs it from equilibrium. These results unveil a nanoscopic view of the interaction between redox protein partners in electron transport chains and its mechanisms of regulation.