4R7C

Crystal Structure of CNG mimicking NaK-ETPP mutant cocrystallized with DiMethylammonium

4R7C の概要

• エントリーDOI: 10.2210/pdb4r7c/pdb
• 関連するPDBエントリー: 3K0D 3K0G 4R50 4R6Z
• 分子名称: Potassium channel protein, GLYCINE, (4S)-2-METHYL-2,4-PENTANEDIOL, ... (5 entities in total)
• 機能のキーワード: alpha-helical membrane protein, nak-chimera channel in complex with dima+, transport protein
• 由来する生物種: Bacillus cereus ATCC 14579
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 46873.83

構造登録者

De March, M.,Napolitano, L.M.R.,Onesti, S. (登録日: 2014-08-27, 公開日: 2015-07-01, 最終更新日: 2023-09-20)

主引用文献

Napolitano, L.M.,Bisha, I.,De March, M.,Marchesi, A.,Arcangeletti, M.,Demitri, N.,Mazzolini, M.,Rodriguez, A.,Magistrato, A.,Onesti, S.,Laio, A.,Torre, V.
A structural, functional, and computational analysis suggests pore flexibility as the base for the poor selectivity of CNG channels.
Proc.Natl.Acad.Sci.USA, 112:E3619-E3628, 2015

PubMed Abstract: Cyclic nucleotide-gated (CNG) ion channels, despite a significant homology with the highly selective K(+) channels, do not discriminate among monovalent alkali cations and are permeable also to several organic cations. We combined electrophysiology, molecular dynamics (MD) simulations, and X-ray crystallography to demonstrate that the pore of CNG channels is highly flexible. When a CNG mimic is crystallized in the presence of a variety of monovalent cations, including Na(+), Cs(+), and dimethylammonium (DMA(+)), the side chain of Glu66 in the selectivity filter shows multiple conformations and the diameter of the pore changes significantly. MD simulations indicate that Glu66 and the prolines in the outer vestibule undergo large fluctuations, which are modulated by the ionic species and the voltage. This flexibility underlies the coupling between gating and permeation and the poor ionic selectivity of CNG channels.

PubMed: 26100907
DOI: 10.1073/pnas.1503334112

実験手法

X-RAY DIFFRACTION (2.3 Å)