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

McMillan, Duncan G. G., Marritt, Sophie J., Firer-Sherwood, Mackenzie A., Shi, Liang, Richardson, David J., Evans, Stephen D., Elliott, Sean J., Butt, Julea N. and Jeuken, Lars J. C. (2013) Protein–protein interaction regulates the direction of catalysis and electron transfer in a redox enzyme complex. Journal of the American Chemical Society, 135 (28). pp. 10550-10556. ISSN 0002-7863

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Abstract

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.

Item Type:	Article
Faculty \ School:	Faculty of Science > School of Chemistry (former - to 2024) Faculty of Science > School of Biological Sciences
UEA Research Groups:	Faculty of Science > Research Groups > Organisms and the Environment Faculty of Science > Research Groups > Molecular Microbiology Faculty of Science > Research Centres > Centre for Molecular and Structural Biochemistry Faculty of Science > Research Groups > Biophysical Chemistry (former - to 2017) Faculty of Science > Research Groups > Chemistry of Light and Energy Faculty of Science > Research Groups > Chemistry of Life Processes Faculty of Science > Research Groups > Energy Materials Laboratory Faculty of Science > Research Groups > Wolfson Centre for Advanced Environmental Microbiology
Depositing User:	Pure Connector
Date Deposited:	30 Jul 2013 02:24
Last Modified:	19 May 2025 08:34
URI:	https://ueaeprints.uea.ac.uk/id/eprint/43095
DOI:	10.1021/ja405072z

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