Atomistic Details of Charge/Space Competition in the Ca 2+ Selectivity of Ryanodine Receptors

TitleAtomistic Details of Charge/Space Competition in the Ca 2+ Selectivity of Ryanodine Receptors
Publication TypeJournal Article
Year of Publication2021
AuthorsLiu, C, Zhang, A, Yan, N, Song, C
JournalJ Phys Chem Lett
Pagination4286-4291
Date Published2021 Apr 28
ISSN1948-7185
Abstract

Ryanodine receptors (RyRs) are ion channels responsible for the fast release of Ca2+ from the sarco/endoplasmic reticulum to the cytosol and show a selectivity of Ca2+ over monovalent cations. By utilizing a recently developed multisite Ca2+ model in molecular dynamic simulations, we show that multiple cations accumulate in the upper selectivity filter of RyRs, and the small size and high valence of Ca2+ make it preferable to K+ in competition for space in this confined region of negative electrostatic potential. The presence of Ca2+ in the upper selectivity filter significantly increases the energy barrier of K+ permeation, while the presence of K+ has little impact on the Ca2+ permeation. Our results provide the atomistic details of the charge/space competition mechanism for the ion selectivity of RyRs, which ensures the robustness of their Ca2+ release function. The mechanism could be utilized in protein- and nanoengineering for valence selectivity of ion species.

DOI10.1021/acs.jpclett.1c00681
Alternate JournalJ Phys Chem Lett
PubMed ID33909426