EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Structural basis of gating modulation of Kv4 channel complexes.
ジャーナル・号・ページ	Nature, Vol. 599, Issue 7883, Page 158-164, Year 2021
掲載日	2021年9月22日
著者	Yoshiaki Kise / Go Kasuya / Hiroyuki H Okamoto / Daichi Yamanouchi / Kan Kobayashi / Tsukasa Kusakizako / Tomohiro Nishizawa / Koichi Nakajo / Osamu Nureki /
PubMed 要旨	Modulation of voltage-gated potassium (Kv) channels by auxiliary subunits is central to the physiological function of channels in the brain and heart. Native Kv4 tetrameric channels form ...Modulation of voltage-gated potassium (Kv) channels by auxiliary subunits is central to the physiological function of channels in the brain and heart. Native Kv4 tetrameric channels form macromolecular ternary complexes with two auxiliary β-subunits-intracellular Kv channel-interacting proteins (KChIPs) and transmembrane dipeptidyl peptidase-related proteins (DPPs)-to evoke rapidly activating and inactivating A-type currents, which prevent the backpropagation of action potentials. However, the modulatory mechanisms of Kv4 channel complexes remain largely unknown. Here we report cryo-electron microscopy structures of the Kv4.2-DPP6S-KChIP1 dodecamer complex, the Kv4.2-KChIP1 and Kv4.2-DPP6S octamer complexes, and Kv4.2 alone. The structure of the Kv4.2-KChIP1 complex reveals that the intracellular N terminus of Kv4.2 interacts with its C terminus that extends from the S6 gating helix of the neighbouring Kv4.2 subunit. KChIP1 captures both the N and the C terminus of Kv4.2. In consequence, KChIP1 would prevent N-type inactivation and stabilize the S6 conformation to modulate gating of the S6 helices within the tetramer. By contrast, unlike the reported auxiliary subunits of voltage-gated channel complexes, DPP6S interacts with the S1 and S2 helices of the Kv4.2 voltage-sensing domain, which suggests that DPP6S stabilizes the conformation of the S1-S2 helices. DPP6S may therefore accelerate the voltage-dependent movement of the S4 helices. KChIP1 and DPP6S do not directly interact with each other in the Kv4.2-KChIP1-DPP6S ternary complex. Thus, our data suggest that two distinct modes of modulation contribute in an additive manner to evoke A-type currents from the native Kv4 macromolecular complex.
リンク	Nature / PubMed:34552243 / PubMed Central
手法	EM (単粒子)
解像度	2.9 - 4.5 Å
構造データ	31005 7e7z EMDB-31005, PDB-7e7z: CryoEM structure of the human Kv4.2-KChIP1 complex, transmembrane region 手法: EM (単粒子) / 解像度: 3.2 Å 31009 7e83 EMDB-31009, PDB-7e83: CryoEM structure of the human Kv4.2-KChIP1 complex, intracellular region 手法: EM (単粒子) / 解像度: 3.1 Å 31010 7e84 EMDB-31010, PDB-7e84: CryoEM structure of human Kv4.2-KChIP1 complex 手法: EM (単粒子) / 解像度: 3.1 Å 31011 7e87 EMDB-31011, PDB-7e87: CryoEM structure of the human Kv4.2-DPP6S complex, transmembrane and intracellular region 手法: EM (単粒子) / 解像度: 3.4 Å 31012 7e89 EMDB-31012, PDB-7e89: CryoEM structure of human Kv4.2-DPP6S complex, extracellular region 手法: EM (単粒子) / 解像度: 4.0 Å 31013 7e8b EMDB-31013, PDB-7e8b: CryoEM structure of human Kv4.2-DPP6S complex 手法: EM (単粒子) / 解像度: 4.2 Å 31016 7e8e EMDB-31016, PDB-7e8e: CryoEM structure of human Kv4.2-DPP6S-KChIP1 complex, transmembrane and intracellular region 手法: EM (単粒子) / 解像度: 3.9 Å 31018 7e8g EMDB-31018, PDB-7e8g: CryoEM structure of human Kv4.2-DPP6S-KChIP1 complex, extracellular region 手法: EM (単粒子) / 解像度: 4.5 Å 31019 7e8h EMDB-31019, PDB-7e8h: CryoEM structure of human Kv4.2-DPP6S-KChIP1 complex 手法: EM (単粒子) / 解像度: 4.5 Å 31399 7f0j EMDB-31399, PDB-7f0j: CryoEM structure of human Kv4.2 手法: EM (単粒子) / 解像度: 2.9 Å 31433 7f3f EMDB-31433, PDB-7f3f: CryoEM structure of human Kv4.2-KChIP1 complex 手法: EM (単粒子) / 解像度: 3.1 Å
化合物	ChemComp-ZN: Unknown entry
由来	homo sapiens (ヒト) octodon degus (デグー)
キーワード	MEMBRANE PROTEIN / ion channel / complex