Structure and mechanism of the K+/H+ exchanger KefC

Ashutosh Gulati, Surabhi Kokane, Annemarie Perez-Boerema, Claudia Alleva, Pascal F. Meier, Rei Matsuoka and David Drew ()
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Ashutosh Gulati: Stockholm University
Surabhi Kokane: Stockholm University
Annemarie Perez-Boerema: Stockholm University
Claudia Alleva: Stockholm University
Pascal F. Meier: Stockholm University
Rei Matsuoka: Stockholm University
David Drew: Stockholm University

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract Intracellular potassium (K+) homeostasis is fundamental to cell viability. In addition to channels, K+ levels are maintained by various ion transporters. One major family is the proton-driven K+ efflux transporters, which in gram-negative bacteria is important for detoxification and in plants is critical for efficient photosynthesis and growth. Despite their importance, the structure and molecular basis for K+-selectivity is poorly understood. Here, we report ~3.1 Å resolution cryo-EM structures of the Escherichia coli glutathione (GSH)-gated K+ efflux transporter KefC in complex with AMP, AMP/GSH and an ion-binding variant. KefC forms a homodimer similar to the inward-facing conformation of Na+/H+ antiporter NapA. By structural assignment of a coordinated K+ ion, MD simulations, and SSM-based electrophysiology, we demonstrate how ion-binding in KefC is adapted for binding a dehydrated K+ ion. KefC harbors C-terminal regulator of K+ conductance (RCK) domains, as present in some bacterial K+-ion channels. The domain-swapped helices in the RCK domains bind AMP and GSH and they inhibit transport by directly interacting with the ion-transporter module. Taken together, we propose that KefC is activated by detachment of the RCK domains and that ion selectivity exploits the biophysical properties likewise adapted by K+-ion-channels.

Date: 2024
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DOI: 10.1038/s41467-024-49082-7

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