- PDB-7phi: Human voltage-gated potassium channel Kv3.1 (with Zn) -
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基本情報
登録情報
データベース: PDB / ID: 7phi
タイトル
Human voltage-gated potassium channel Kv3.1 (with Zn)
要素
Potassium voltage-gated channel, Shaw-related subfamily, member 1
キーワード
TRANSPORT PROTEIN / Channel / potassium channel / tetramer / voltage-gated / membrane protein
機能・相同性
機能・相同性情報
response to nerve growth factor / globus pallidus development / response to auditory stimulus / response to fibroblast growth factor / response to potassium ion / corpus callosum development / delayed rectifier potassium channel activity / voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / positive regulation of potassium ion transmembrane transport / Voltage gated Potassium channels ...response to nerve growth factor / globus pallidus development / response to auditory stimulus / response to fibroblast growth factor / response to potassium ion / corpus callosum development / delayed rectifier potassium channel activity / voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / positive regulation of potassium ion transmembrane transport / Voltage gated Potassium channels / response to light intensity / optic nerve development / neuronal cell body membrane / response to amine / kinesin binding / action potential / voltage-gated potassium channel activity / axolemma / voltage-gated potassium channel complex / axon terminus / dendrite membrane / potassium ion transmembrane transport / calyx of Held / cerebellum development / protein tetramerization / potassium ion transport / protein homooligomerization / response to toxic substance / cellular response to xenobiotic stimulus / presynaptic membrane / transmembrane transporter binding / postsynaptic membrane / cell surface / plasma membrane 類似検索 - 分子機能
Potassium channel, voltage dependent, Kv3.1 / Potassium channel, voltage dependent, Kv3 / Potassium channel, voltage dependent, Kv / Potassium channel tetramerisation-type BTB domain / BTB/POZ domain / Voltage-gated potassium channel / Potassium Channel Kv1.1; Chain A / Potassium Channel Kv1.1; Chain A / Broad-Complex, Tramtrack and Bric a brac / Voltage-dependent channel domain superfamily ...Potassium channel, voltage dependent, Kv3.1 / Potassium channel, voltage dependent, Kv3 / Potassium channel, voltage dependent, Kv / Potassium channel tetramerisation-type BTB domain / BTB/POZ domain / Voltage-gated potassium channel / Potassium Channel Kv1.1; Chain A / Potassium Channel Kv1.1; Chain A / Broad-Complex, Tramtrack and Bric a brac / Voltage-dependent channel domain superfamily / BTB/POZ domain / SKP1/BTB/POZ domain superfamily / Ion transport domain / Ion transport protein / 2-Layer Sandwich / Alpha Beta 類似検索 - ドメイン・相同性
ジャーナル: Nat Commun / 年: 2022 タイトル: Cryo-EM structure of the human Kv3.1 channel reveals gating control by the cytoplasmic T1 domain. 著者: Gamma Chi / Qiansheng Liang / Akshay Sridhar / John B Cowgill / Kasim Sader / Mazdak Radjainia / Pu Qian / Pablo Castro-Hartmann / Shayla Venkaya / Nanki Kaur Singh / Gavin McKinley / ...著者: Gamma Chi / Qiansheng Liang / Akshay Sridhar / John B Cowgill / Kasim Sader / Mazdak Radjainia / Pu Qian / Pablo Castro-Hartmann / Shayla Venkaya / Nanki Kaur Singh / Gavin McKinley / Alejandra Fernandez-Cid / Shubhashish M M Mukhopadhyay / Nicola A Burgess-Brown / Lucie Delemotte / Manuel Covarrubias / Katharina L Dürr / 要旨: Kv3 channels have distinctive gating kinetics tailored for rapid repolarization in fast-spiking neurons. Malfunction of this process due to genetic variants in the KCNC1 gene causes severe epileptic ...Kv3 channels have distinctive gating kinetics tailored for rapid repolarization in fast-spiking neurons. Malfunction of this process due to genetic variants in the KCNC1 gene causes severe epileptic disorders, yet the structural determinants for the unusual gating properties remain elusive. Here, we present cryo-electron microscopy structures of the human Kv3.1a channel, revealing a unique arrangement of the cytoplasmic tetramerization domain T1 which facilitates interactions with C-terminal axonal targeting motif and key components of the gating machinery. Additional interactions between S1/S2 linker and turret domain strengthen the interface between voltage sensor and pore domain. Supported by molecular dynamics simulations, electrophysiological and mutational analyses, we identify several residues in the S4/S5 linker which influence the gating kinetics and an electrostatic interaction between acidic residues in α6 of T1 and R449 in the pore-flanking S6T helices. These findings provide insights into gating control and disease mechanisms and may guide strategies for the design of pharmaceutical drugs targeting Kv3 channels.