Protein–protein interaction regulates the direction of catalysis and electron transfer in a redox enzyme complex

Duncan G. G. McMillan, Sophie J. Marritt, Mackenzie A. Firer-Sherwood, Liang Shi, David J. Richardson, Stephen D. Evans, Sean J. Elliott, Julea N. Butt, Lars J. C. Jeuken

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64 Citations (Scopus)


Protein–protein interactions are well-known to regulate enzyme activity in cell signaling and metabolism. Here, we show that protein–protein interactions regulate the activity of a respiratory-chain enzyme, CymA, by changing the direction or bias of catalysis. CymA, a member of the widespread NapC/NirT superfamily, is a menaquinol-7 (MQ-7) dehydrogenase that donates electrons to several distinct terminal reductases in the versatile respiratory network of Shewanella oneidensis. We report the incorporation of CymA within solid-supported membranes that mimic the inner membrane architecture of S. oneidensis. Quartz-crystal microbalance with dissipation (QCM-D) resolved the formation of a stable complex between CymA and one of its native redox partners, flavocytochrome c3 (Fcc3) fumarate reductase. Cyclic voltammetry revealed that CymA alone could only reduce MQ-7, while the CymA-Fcc3 complex catalyzed the reaction required to support anaerobic respiration, the oxidation of MQ-7. We propose that MQ-7 oxidation in CymA is limited by electron transfer to the hemes and that complex formation with Fcc3 facilitates the electron-transfer rate along the heme redox chain. These results reveal a yet unexplored mechanism by which bacteria can regulate multibranched respiratory networks through protein–protein interactions.
Original languageEnglish
Pages (from-to)10550-10556
Number of pages7
JournalJournal of the American Chemical Society
Issue number28
Publication statusPublished - 25 Jun 2013

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