The di-heme family of respiratory complex II enzymes

• Progress in characterization of diverse di-heme complex-II family members.
• Evidence for electrogenic catalysis by di-heme succinate:menaquinone reductases.
• Evidence for electroneutral catalysis by di-heme menaquinol:fumarate reductases.
• Water is an essential feature of transmembrane proton transfer via the “E-pathway”.
• Bifurcation of the E-pathway via transient His-heme propionate H-bonded interaction.

The di-heme family of succinate:quinone oxidoreductases is of particular interest, because its members support electron transfer across the biological membranes in which they are embedded. In the case of the di-heme-containing succinate:menaquinone reductase (SQR) from Gram-positive bacteria and other menaquinone-containing bacteria, this results in an electrogenic reaction. This is physiologically relevant in that it allows the transmembrane electrochemical proton potential Δp to drive the endergonic oxidation of succinate by menaquinone. In the case of the reverse reaction, menaquinol oxidation by fumarate, catalysed by the di-heme-containing quinol:fumarate reductase (QFR), evidence has been obtained that this electrogenic electron transfer reaction is compensated by proton transfer via a both novel and essential transmembrane proton transfer pathway (“E-pathway”). Although the reduction of fumarate by menaquinol is exergonic, it is obviously not exergonic enough to support the generation of a Δp. This compensatory “E-pathway” appears to be required by all di-heme-containing QFR enzymes and results in the overall reaction being electroneutral. In addition to giving a brief overview of progress in the characterization of other members of this diverse family, this contribution summarizes key evidence and progress in identifying constituents of the “E-pathway” within the framework of the crystal structure of the QFR from the anaerobic epsilon-proteobacterium Wolinella succinogenes at 1.78 Å resolution. This article is part of a Special Issue entitled: Respiratory complex II: Role in cellular physiology and disease.