8SD3

CryoEM structure of rat Kv2.1(1-598) wild type in nanodiscs

8SD3 の概要

• エントリーDOI: 10.2210/pdb8sd3/pdb
• EMDBエントリー: 40349
• 分子名称: Potassium voltage-gated channel subfamily B member 1, (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate, POTASSIUM ION (3 entities in total)
• 機能のキーワード: voltage-dependent potassium channel, membrane protein
• 由来する生物種: Rattus norvegicus (Norway rat)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 292766.62

構造登録者

Tan, X.,Swartz, K.J. (登録日: 2023-04-06, 公開日: 2023-09-27, 最終更新日: 2023-10-25)

主引用文献

Fernandez-Marino, A.I.,Tan, X.F.,Bae, C.,Huffer, K.,Jiang, J.,Swartz, K.J.
Inactivation of the Kv2.1 channel through electromechanical coupling.
Nature, 622:410-417, 2023

PubMed Abstract: The Kv2.1 voltage-activated potassium (Kv) channel is a prominent delayed-rectifier Kv channel in the mammalian central nervous system, where its mechanisms of activation and inactivation are critical for regulating intrinsic neuronal excitability. Here we present structures of the Kv2.1 channel in a lipid environment using cryo-electron microscopy to provide a framework for exploring its functional mechanisms and how mutations causing epileptic encephalopathies alter channel activity. By studying a series of disease-causing mutations, we identified one that illuminates a hydrophobic coupling nexus near the internal end of the pore that is critical for inactivation. Both functional and structural studies reveal that inactivation in Kv2.1 results from dynamic alterations in electromechanical coupling to reposition pore-lining S6 helices and close the internal pore. Consideration of these findings along with available structures for other Kv channels, as well as voltage-activated sodium and calcium channels, suggests that related mechanisms of inactivation are conserved in voltage-activated cation channels and likely to be engaged by widely used therapeutics to achieve state-dependent regulation of channel activity.

PubMed: 37758949
DOI: 10.1038/s41586-023-06582-8

実験手法

ELECTRON MICROSCOPY (2.95 Å)