| Literature DB >> 30158697 |
Hideaki E Kato1,2, Yoon Seok Kim3,4,5, Joseph M Paggi6,7, Kathryn E Evans3,4,5, William E Allen3,4,5, Claire Richardson6, Keiichi Inoue8,9,10, Shota Ito9, Charu Ramakrishnan3,4,5, Lief E Fenno3,4,5, Keitaro Yamashita11, Daniel Hilger12, Soo Yeun Lee3,4,5, Andre Berndt3,4,5, Kang Shen13,5, Hideki Kandori9,10, Ron O Dror6,7, Brian K Kobilka12, Karl Deisseroth14,15,16.
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.Entities:
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Year: 2018 PMID： 30158697 PMCID： PMC6317992 DOI： 10.1038/s41586-018-0504-5
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 49.962