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Mechanism of Kch activation by Zn2+

Aug 2026 · PNAS Nexus · Vol 5 · 0 citations · 54 references
Medicine

Abstract

Abstract Escherichia coli has a single K+ channel gene, kch, that produces a K+ channel with six transmembrane segments and a cytosolic Regulate Conductance of K+ channels (RCK) domain. RCK domains are present in both eukaryotic and prokaryotic organisms and known to regulate ion channel activity upon binding of an ion or a nucleotide, however, how Kch is regulated remains unknown. Here, we show that Zn2+ or Cu2+ activates Kch via the RCK domain. Structural studies reveal that eight RCK domains assemble into a gating ring that can assume three conformations, closed, intermediate, and open, and that Zn2+ promotes the open conformation by stabilizing the assembly interface. These results expand our knowledge on Kch and on RCK-mediated regulation of ion channels.

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