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Phosphorylation disrupts long-distance electron transport in cytochrome c

IIQ

Gomila AMJ*, Pérez-Mejías G*, Nin-Hill A*, Guerra-Castellano A, Casas-Ferrer L, Ortiz-Tescari S, Díaz-Quintana A, Samitier J, Rovira C, De la Rosa MA, Díaz-Moreno I, Gorostiza P, Giannotti MI, Lagunas A. Nature Communications 2022, Vol. 13, 7100

It has been recently shown that electron transfer between mitochondrial cytochrome c and the cytochrome c1 subunit of the cytochrome bc1 and cytochrome c 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 c1 and cytochrome c or the phosphomimetic Y48pCMF 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.

 

https://doi.org/10.1038/s41467-022-34809-1

 

Gonzalo Pérez Mejías