Structure of the gating domain of a Ca²⁺-activated K⁺ channel complexed with Ca²⁺/calmodulin

Small-conductance Ca²⁺-activated K⁺ channels (SK channels)^1,2 are independent of voltage and gated solely by intracellular Ca²⁺. These membrane channels are heteromeric complexes that comprise pore-forming α-subunits and the Ca²⁺-binding protein calmodulin (CaM). CaM binds to the SK channel through the CaM-binding domain (CaMBD), which is located in an intracellular region of the α-subunit immediately carboxy-terminal to the pore^3,4. Channel opening is triggered when Ca²⁺ binds the EF hands in the N-lobe of CaM⁴. Here we report the 1.60 Å crystal structure of the SK channel CaMBD/Ca²⁺/CaM complex. The CaMBD forms an elongated dimer with a CaM molecule bound at each end; each CaM wraps around three α-helices, two from one CaMBD subunit and one from the other. As only the CaM N-lobe has bound Ca²⁺, the structure provides a view of both calcium-dependent and -independent CaM/protein interactions. Together with biochemical data, the structure suggests a possible gating mechanism for the SK channel.