8AYP

NaK C-DI mutant with Rb+ and Ba2+

8AYP の概要

• エントリーDOI: 10.2210/pdb8ayp/pdb
• 分子名称: Potassium channel protein, (4S)-2-METHYL-2,4-PENTANEDIOL, RUBIDIUM ION, ... (5 entities in total)
• 機能のキーワード: ion channel, prokaryote, membrane protein, 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: 47261.05

構造登録者

Minniberger, S.,Plested, A.J.R. (登録日: 2022-09-02, 公開日: 2023-02-22, 最終更新日: 2024-02-07)

主引用文献

Schackert, F.K.,Biedermann, J.,Abdolvand, S.,Minniberger, S.,Song, C.,Plested, A.J.R.,Carloni, P.,Sun, H.
Mechanism of Calcium Permeation in a Glutamate Receptor Ion Channel.
J.Chem.Inf.Model., 63:1293-1300, 2023

PubMed Abstract: The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are neurotransmitter-activated cation channels ubiquitously expressed in vertebrate brains. The regulation of calcium flux through the channel pore by RNA-editing is linked to synaptic plasticity while excessive calcium influx poses a risk for neurodegeneration. Unfortunately, the molecular mechanisms underlying this key process are mostly unknown. Here, we investigated calcium conduction in calcium-permeable AMPAR using Molecular Dynamics (MD) simulations with recently introduced multisite force-field parameters for Ca. Our calculations are consistent with experiment and explain the distinct calcium permeability in different RNA-edited forms of GluA2. For one of the identified metal binding sites, multiscale Quantum Mechanics/Molecular Mechanics (QM/MM) simulations further validated the results from MD and revealed small but reproducible charge transfer between the metal ion and its first solvation shell. In addition, the ion occupancy derived from MD simulations independently reproduced the Ca binding profile in an X-ray structure of an NaK channel mimicking the AMPAR selectivity filter. This integrated study comprising X-ray crystallography, multisite MD, and multiscale QM/MM simulations provides unprecedented insights into Ca permeation mechanisms in AMPARs, and paves the way for studying other biological processes in which Ca plays a pivotal role.

PubMed: 36758214
DOI: 10.1021/acs.jcim.2c01494

実験手法

X-RAY DIFFRACTION (2.1 Å)