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The gating ring-forming RCK domain regulates channel gating in response to various cellular chemical stimuli in eukaryotic Slo channel families and the majority of ligand-gated prokaryotic K +  channels and transporters. Here we present structural and functional studies of a dual RCK-containing, multi-ligand gated K +  channel from  Geobacter sulfurreducens , named GsuK. We demonstrate that ADP and NAD +  activate the GsuK channel, whereas Ca 2+  serves as an allosteric inhibitor. Multiple crystal structures elucidate the structural basis of multi-ligand gating in GsuK, and also reveal a unique ion conduction pore with segmented inner helices. Structural comparison leads us to propose a novel pore opening mechanics that is distinct from other K +  channels.

Distinct gating mechanisms revealed by the structures of a multi-ligand gated K + channel