Structure of the gating domain of a Ca.sup.2+-activated K.sup.+ channel complexed with Ca.sup.2+/calmodulin

Small-conductance Ca.sup.2+-activated K.sup.+ channels (SK channels).sup.1,2 are independent of voltage and gated solely by intracellular Ca.sup.2+. These membrane channels are heteromeric complexes that comprise pore-forming [alpha]-subunits and the Ca.sup.2+-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 [alpha]-subunit immediately carboxy-terminal to the pore.sup.3,4. Channel opening is triggered when Ca.sup.2+ binds the EF hands in the N-lobe of CaM.sup.4. Here we report the 1.60 Å crystal structure of the SK channel CaMBD/Ca.sup.2+/CaM complex. The CaMBD forms an elongated dimer with a CaM molecule bound at each end; each CaM wraps around three [alpha]-helices, two from one CaMBD subunit and one from the other. As only the CaM N-lobe has bound Ca.sup.2+, 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.