9NES

C-terminal mVenues tagged Shaker TM domain in C4 symmetry

9NES の概要

• エントリーDOI: 10.2210/pdb9nes/pdb
• EMDBエントリー: 49333
• 分子名称: Potassium voltage-gated channel protein Shaker, (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate, POTASSIUM ION, ... (4 entities in total)
• 機能のキーワード: voltage-gated potassium channel, membrane protein
• 由来する生物種: Drosophila melanogaster (fruit fly)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 326240.10

構造登録者

Tan, X.,Swartz, K.J. (登録日: 2025-02-20, 公開日: 2025-08-06, 最終更新日: 2025-10-08)

主引用文献

Tan, X.F.,Fernandez-Marino, A.I.,Li, Y.,Chang, T.H.,Swartz, K.J.
Structural basis of fast N-type inactivation in K v channels.
Nature, 645:1081-1089, 2025

PubMed Abstract: Action potentials are generated by opening of voltage-activated sodium (Na) and potassium (K) channels, which can rapidly inactivate to shape the nerve impulse and contribute to synaptic facilitation and short-term memory. The mechanism of fast inactivation was proposed to involve an intracellular domain that blocks the internal pore in both Na and K channels; however, recent studies in Na and K channels support a mechanism in which the internal pore closes during inactivation. Here we investigate the mechanism of fast inactivation in the Shaker K channel using cryo-electron microscopy, mass spectrometry and electrophysiology. We resolved structures of a fully inactivated state in which the non-polar end of the N terminus plugs the internal pore in an extended conformation. The N-terminal methionine is deleted, leaving an alanine that is acetylated and interacts with a pore-lining isoleucine residue where RNA editing regulates fast inactivation. Opening of the internal activation gate is required for fast inactivation because it enables the plug domain to block the pore and repositions gate residues to interact with and stabilize that domain. We also show that external K destabilizes the inactivated state by altering the conformation of the ion selectivity filter rather than by electrostatic repulsion. These findings establish the mechanism of fast inactivation in K channels, revealing how it is regulated by RNA editing and N-terminal acetylation, and providing a framework for understanding related mechanisms in other voltage-activated channels.

PubMed: 40770100
DOI: 10.1038/s41586-025-09339-7

実験手法

ELECTRON MICROSCOPY (2.67 Å)