Key result
Cd(2+) coordination at V319C and A316C in the BK inner pore reveals a sharper kink in the S6 inner helix than in Kv channels and suggests the absence of a cytosolic ion permeation gate.
The study highlights fundamental structural differences between BK and Kv channels in their inner pore region, which likely underlie differences in voltage-dependent gating.
Distinguishes BK from Kv channel architecture; challenges conserved gating models and leaves clinical translation open.
To probe structure and gating-associated conformational changes in BK-type potassium (BK) channels, we examined consequences of Cd(2+) coordination with cysteines introduced at two positions in the BK inner pore. At V319C, the equivalent of valine in the conserved Kv proline-valine-proline (PVP) motif, Cd(2+) forms intrasubunit coordination with a native glutamate E321, which would place the side chains of V319C and E321 much closer together than observed in voltage-dependent K(+) (Kv) channel structures, requiring that the proline between V319C and E321 introduces a kink in the BK S6 inner helix sharper than that observed in Kv channel structures. At inner pore position A316C, Cd(2+) binds with modest state dependence, suggesting the absence of an ion permeation gate at the cytosolic side of BK channel. These results highlight fundamental structural differences between BK and Kv channels in their inner pore region, which likely underlie differences in voltage-dependent gating between these channels.
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Zhou et al. (2015) studied this question. Cd(2+) coordination with introduced cysteines (V319C and A316C) was evaluated on Structure and gating-associated conformational changes in BK-type potassium channels. Cd(2+) coordination at V319C and A316C in the BK inner pore reveals a sharper kink in the S6 inner helix than in Kv channels and suggests the absence of a cytosolic ion permeation gate.
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