9M05

Cryo-EM structure of dVGAC complexed with iodide

9M05 の概要

• エントリーDOI: 10.2210/pdb9m05/pdb
• 関連するPDBエントリー: 8YQ5 8YQ6
• EMDBエントリー: 39496 39497 63538
• 分子名称: de novo designed ion channel, IODIDE ION (2 entities in total)
• 機能のキーワード: de novo design, ion channels, de novo protein
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 132375.64

構造登録者

Lu, P.L.,Zhou, C. (登録日: 2025-02-23, 公開日: 2025-10-29, 最終更新日: 2026-01-07)

主引用文献

Zhou, C.,Li, H.,Wang, J.,Qian, C.,Xiong, H.,Chu, Z.,Shao, Q.,Li, X.,Sun, S.,Sun, K.,Zhu, A.,Wang, J.,Jin, X.,Yang, F.,Gamal El-Din, T.M.,Li, B.,Huang, J.,Wu, K.,Lu, P.
De novo designed voltage-gated anion channels suppress neuron firing.
Cell, 188:7495-, 2025

PubMed Abstract: Design of ion channels responsive to environmental cues has significant implications in modulating cellular activities and sensor development, but it remains a significant challenge due to the complexities involved in designing stimuli-induced conformational changes in proteins. Here, we report the accurate de novo design of voltage-gated anion channels, namely dVGACs. dVGACs adopt a 15-helix pentameric architecture featuring arginine constrictions within the transmembrane span and show voltage-dependent anions currents in patch-clamp experiments. Cryo-electron microscopy (cryo-EM) structures of dVGACs closely align with the design models. Cryo-EM structures and molecular dynamics simulations suggest that the arginine constrictions undergo voltage-induced conformational changes, serving as both a voltage sensor and a selectivity filter as designed. Notably, the anion selectivity and voltage sensitivity of dVGACs can be tuned through targeted mutations for suppressing neuronal firing in situ. The ability to create ion channels with custom-designed conformational changes refreshes our insights into membrane biophysics and unveils diverse potential applications.

PubMed: 41106381
DOI: 10.1016/j.cell.2025.09.023

実験手法

ELECTRON MICROSCOPY (3.72 Å)