6ZGD

GLIC pentameric ligand-gated ion channel, pH 7

6ZGD の概要

• エントリーDOI: 10.2210/pdb6zgd/pdb
• EMDBエントリー: 11202
• 分子名称: Proton-gated ion channel (1 entity in total)
• 機能のキーワード: glic, pentameric ligand-gated ion channel, cryoem, membrane protein
• 由来する生物種: Gloeobacter violaceus (strain ATCC 29082 / PCC 7421)
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 181458.75

構造登録者

Rovsnik, U.,Zhuang, Y.,Forsberg, B.O.,Carroni, M.,Yvonnesdotter, L.,Howard, R.J.,Lindahl, E. (登録日: 2020-06-18, 公開日: 2021-05-26, 最終更新日: 2024-07-10)

主引用文献

Rovsnik, U.,Zhuang, Y.,Forsberg, B.O.,Carroni, M.,Yvonnesdotter, L.,Howard, R.J.,Lindahl, E.
Dynamic closed states of a ligand-gated ion channel captured by cryo-EM and simulations.
Life Sci Alliance, 4:-, 2021

PubMed Abstract: Ligand-gated ion channels are critical mediators of electrochemical signal transduction across evolution. Biophysical and pharmacological characterization of these receptor proteins relies on high-quality structures in multiple, subtly distinct functional states. However, structural data in this family remain limited, particularly for resting and intermediate states on the activation pathway. Here, we report cryo-electron microscopy (cryo-EM) structures of the proton-activated ligand-gated ion channel (GLIC) under three pH conditions. Decreased pH was associated with improved resolution and side chain rearrangements at the subunit/domain interface, particularly involving functionally important residues in the β1-β2 and M2-M3 loops. Molecular dynamics simulations substantiated flexibility in the closed-channel extracellular domains relative to the transmembrane ones and supported electrostatic remodeling around E35 and E243 in proton-induced gating. Exploration of secondary cryo-EM classes further indicated a low-pH population with an expanded pore. These results allow us to define distinct protonation and activation steps in pH-stimulated conformational cycling in GLIC, including interfacial rearrangements largely conserved in the pentameric channel family.

PubMed: 34210687
DOI: 10.26508/lsa.202101011

実験手法

ELECTRON MICROSCOPY (4.1 Å)