Activation mechanism of a human SK-calmodulin channel complex elucidated by cryo-EM structures.

ABSTRACT: Small-conductance Ca²⁺-activated K⁺ (SK) channels mediate neuron excitability and are associated with synaptic transmission and plasticity. They also regulate immune responses and the size of blood cells. Activation of SK channels requires calmodulin (CaM), but how CaM binds and opens SK channels has been unclear. Here we report cryo-electron microscopy (cryo-EM) structures of a human SK4-CaM channel complex in closed and activated states at 3.4- and 3.5-angstrom resolution, respectively. Four CaM molecules bind to one channel tetramer. Each lobe of CaM serves a distinct function: The C-lobe binds to the channel constitutively, whereas the N-lobe interacts with the S4-S5 linker in a Ca²⁺-dependent manner. The S4-S5 linker, which contains two distinct helice

SUBMITTER: Lee CH 

PROVIDER: S-EPMC6241251 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature