EMD-7539

Single-particle
4.7 Å
EMD-7539 Deposition: 08/03/2018
Map released: 02/05/2018
Last modified: 13/03/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-7539

Cryo-EM structure of the human SK4/calmodulin channel complex in the Ca2+ bound state II

EMD-7539

Single-particle
4.7 Å
EMD-7539 Deposition: 08/03/2018
Map released: 02/05/2018
Last modified: 13/03/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens
Sample: human SK4/calmodulin channel complex
Fitted models: 6cno (Avg. Q-score: 0.236)

Deposition Authors: Lee CH , MacKinnon R
Activation mechanism of a human SK-calmodulin channel complex elucidated by cryo-EM structures.
Lee CH , MacKinnon R
(2018) Science , 360 , 508 - 513
PUBMED: 29724949
DOI: doi:10.1126/science.aas9466
ISSN: 1095-9203
ASTM: SCIEAS
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 helices, undergoes conformational changes upon CaM binding to open the channel pore. These structures reveal the gating mechanism of SK channels and provide a basis for understanding SK channel pharmacology.