Proton translocation by transhydrogenase

Transhydrogenase is a membrane protein that participates in the chemiosmotic proton circuit of mitochondria and bacteria. It has membrane-peripheral components that catalyse the redox reaction, and a membrane-spanning component that translocates hydrogen ions. At the 126th Nobel Symposium (Örsundsbro, 2003) recent X-ray structures of the peripheral components were described in the context of the likely mechanism by which the redox reaction is energetically coupled to proton translocation across the membrane. A review of the mechanism of proton translocation by transhydrogenase was recently published [1] and a summary of this article is featured below (1, 2). Transhydrogenase, in animal mitochondria and bacteria, couples hydride transfer between NADH and NADP+ to proton translocation across a membrane. Within the protein, the redox reaction occurs at some distance from the proton-translocation pathway and coupling is achieved through conformational changes. In an ‘open’ conformation of transhydrogenase, in which substrate nucleotides bind and product nucleotides dissociate, the dihydronicotinamide and nicotinamide rings are held apart to block hydride transfer; in an ‘occluded’ conformation, they are moved into apposition to permit the redox chemistry. In the two monomers of transhydrogenase, there is a reciprocating, out-of-phase alternation of these conformations during turnover.