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-Structure paper
タイトル | Structure and mechanism of the K/H exchanger KefC. |
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ジャーナル・号・ページ | Nat Commun, Vol. 15, Issue 1, Page 4751, Year 2024 |
掲載日 | 2024年6月4日 |
著者 | Ashutosh Gulati / Surabhi Kokane / Annemarie Perez-Boerema / Claudia Alleva / Pascal F Meier / Rei Matsuoka / David Drew / |
PubMed 要旨 | 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 ...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. |
リンク | Nat Commun / PubMed:38834573 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.16 - 3.18 Å |
構造データ | EMDB-16318: Structure of the K/H exchanger KefC EMDB-16319: Structure of the K+/H+ exchanger KefC with GSH |
化合物 | ChemComp-K: ChemComp-AMP: ChemComp-PGW: ChemComp-GSH: |
由来 |
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キーワード | MEMBRANE PROTEIN / potassium proton exchanger / KefC / Transporter / CPA / GSH |