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-Structure paper
タイトル | Activation mechanism of a human SK-calmodulin channel complex elucidated by cryo-EM structures. |
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ジャーナル・号・ページ | Science, Vol. 360, Issue 6388, Page 508-513, Year 2018 |
掲載日 | 2018年5月4日 |
著者 | Chia-Hsueh Lee / Roderick MacKinnon / |
PubMed 要旨 | 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 ...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. |
リンク | Science / PubMed:29724949 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.4 - 4.7 Å |
構造データ | EMDB-7537, PDB-6cnm: |
化合物 | ChemComp-K: ChemComp-POV: ChemComp-LMT: ChemComp-CA: |
由来 |
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キーワード | MEMBRANE PROTEIN / ion channel / neuroscience / calmodulin |