Redox-state sensing by hydrogen bonds in the CuA center of cytochrome c oxidase

Abstract

Cytochrome c oxidases (CcO) couple electron transfer to active proton translocation through a gated mechanism that minimizes energy losses by preventing protons from flowing backwards or leaking. Such a complex mechanism requires that information about the redox and protonation states of the different centers be transmitted between different parts of the oxidase. Here we report a network of residues located around the electron entry point of CcO, the CuA site in subunit II, that experience collective pH equilibria around neutral pH. This network starts at the occluded side of the CuA site and extends to the interface between subunits I and II of the CcO, where the proton exit is located and through which electrons flow into subunit I. One of the residues in this network is directly involved in a hydrogen bond to one of the CuA ligands, whose strength is highly sensitive to the redox state of the metal center. We propose that this interaction mediates the transmission of redox changes from ET centers to other functional regions of the oxidase, and possibly also in other similar machineries, as part of their gating and regulatory mechanisms.