Structural mechanisms of selectivity and gating in anion channelrhodopsins.

Nature
Hideaki E KatoKarl Deisseroth

Abstract

Both designed and natural anion-conducting channelrhodopsins (dACRs and nACRs, respectively) have been widely applied in optogenetics (enabling selective inhibition of target-cell activity during animal behaviour studies), but each class exhibits performance limitations, underscoring trade-offs in channel structure-function relationships. Therefore, molecular and structural insights into dACRs and nACRs will be critical not only for understanding the fundamental mechanisms of these light-gated anion channels, but also to create next-generation optogenetic tools. Here we report crystal structures of the dACR iC++, along with spectroscopic, electrophysiological and computational analyses that provide unexpected insights into pH dependence, substrate recognition, channel gating and ion selectivity of both dACRs and nACRs. These results enabled us to create an anion-conducting channelrhodopsin integrating the key features of large photocurrent and fast kinetics alongside exclusive anion selectivity.

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Citations

Apr 11, 2019·Journal of Neural Engineering·Ilya KolbCraig R Forest
Jul 17, 2020·Chemical Society Reviews·Yin FangBozhi Tian
Oct 2, 2019·Frontiers in Physiology·Emily A FerencziChristopher L-H Huang
Jul 20, 2019·Science·James H MarshelKarl Deisseroth
Feb 18, 2020·Biophysics Reviews·Hideki Kandori
Feb 20, 2020·Critical Reviews in Biochemistry and Molecular Biology·Xiang XuXiaofeng Jia
Nov 13, 2020·Nature Communications·Dmitrii ZabelskiiValentin Gordeliy
May 1, 2020·Nano Research·Jiuyun ShiBozhi Tian
Aug 26, 2020·Chemical Reviews·Charlotte I LynchMark S P Sansom
Sep 4, 2021·Journal of Synchrotron Radiation·Seiki BabaKunio Hirata

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Methods Mentioned

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