Structural mechanisms of selectivity and gating in anion channelrhodopsins

Hideaki E. Kato (), Yoon Seok Kim, Joseph M. Paggi, Kathryn E. Evans, William E. Allen, Claire Richardson, Keiichi Inoue, Shota Ito, Charu Ramakrishnan, Lief E. Fenno, Keitaro Yamashita, Daniel Hilger, Soo Yeun Lee, Andre Berndt, Kang Shen, Hideki Kandori, Ron O. Dror, Brian K. Kobilka and Karl Deisseroth ()
Additional contact information
Hideaki E. Kato: Stanford University School of Medicine
Yoon Seok Kim: Stanford University
Joseph M. Paggi: Stanford University
Kathryn E. Evans: Stanford University
William E. Allen: Stanford University
Claire Richardson: Stanford University
Keiichi Inoue: PRESTO, Japan Science and Technology Agency
Shota Ito: Nagoya Institute of Technology
Charu Ramakrishnan: Stanford University
Lief E. Fenno: Stanford University
Keitaro Yamashita: RIKEN SPring-8 Center
Daniel Hilger: Stanford University School of Medicine
Soo Yeun Lee: Stanford University
Andre Berndt: Stanford University
Kang Shen: Stanford University
Hideki Kandori: Nagoya Institute of Technology
Ron O. Dror: Stanford University
Brian K. Kobilka: Stanford University School of Medicine
Karl Deisseroth: Stanford University

Nature, 2018, vol. 561, issue 7723, 349-354

Abstract: 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.

Keywords: Optogenetic; Anion Selectivity; Photocurrent Magnitude; Vreven; Photocurrent Amplitude (search for similar items in EconPapers)
Date: 2018
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DOI: 10.1038/s41586-018-0504-5

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