6CNN

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

6CNN の概要

• エントリーDOI: 10.2210/pdb6cnn/pdb
• EMDBエントリー: 7537 7538 7539
• 分子名称: Intermediate conductance calcium-activated potassium channel protein 4, Calmodulin-1, POTASSIUM ION, ... (6 entities in total)
• 機能のキーワード: ion channel, neuroscience, calmodulin, membrane protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 266206.72

構造登録者

Lee, C.H.,MacKinnon, R. (登録日: 2018-03-08, 公開日: 2018-05-02, 最終更新日: 2024-03-13)

主引用文献

Lee, C.H.,MacKinnon, R.
Activation mechanism of a human SK-calmodulin channel complex elucidated by cryo-EM structures.
Science, 360:508-513, 2018

PubMed Abstract: Small-conductance Ca-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 Ca-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.

PubMed: 29724949
DOI: 10.1126/science.aas9466

実験手法

ELECTRON MICROSCOPY (3.5 Å)