8BY2

Structure of the K+/H+ exchanger KefC with GSH.

Summary for 8BY2

• Entry DOI: 10.2210/pdb8by2/pdb
• Related: 8BXG
• EMDB information: 16319
• Descriptor: Glutathione-regulated potassium-efflux system protein KefC, POTASSIUM ION, ADENOSINE MONOPHOSPHATE, ... (5 entities in total)
• Functional Keywords: potassium proton exchanger, kefc, transporter, cpa, membrane protein, gsh
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 125251.74

Authors

Gulati, A.,Drew, D. (deposition date: 2022-12-11, release date: 2023-12-27, Last modification date: 2024-06-19)

Primary citation

Gulati, A.,Kokane, S.,Perez-Boerema, A.,Alleva, C.,Meier, P.F.,Matsuoka, R.,Drew, D.
Structure and mechanism of the K + /H + exchanger KefC.
Nat Commun, 15:4751-4751, 2024

PubMed 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.

PubMed: 38834573
DOI: 10.1038/s41467-024-49082-7

Experimental method

ELECTRON MICROSCOPY (3.18 Å)