Crystal structure of the natural anion-conducting channelrhodopsin GtACR1

Yoon Seok Kim, Hideaki E. Kato (), Keitaro Yamashita, Shota Ito, Keiichi Inoue, Charu Ramakrishnan, Lief E. Fenno, Kathryn E. Evans, Joseph M. Paggi, Ron O. Dror, Hideki Kandori, Brian K. Kobilka and Karl Deisseroth ()
Additional contact information
Yoon Seok Kim: and Howard Hughes Medical Institute, Stanford University
Hideaki E. Kato: Stanford University School of Medicine
Keitaro Yamashita: RIKEN SPring-8 Center
Shota Ito: Nagoya Institute of Technology
Keiichi Inoue: Japan Science and Technology Agency, Honcho
Charu Ramakrishnan: and Howard Hughes Medical Institute, Stanford University
Lief E. Fenno: and Howard Hughes Medical Institute, Stanford University
Kathryn E. Evans: and Howard Hughes Medical Institute, Stanford University
Joseph M. Paggi: Stanford University
Ron O. Dror: Stanford University
Hideki Kandori: Nagoya Institute of Technology
Brian K. Kobilka: Stanford University School of Medicine
Karl Deisseroth: and Howard Hughes Medical Institute, Stanford University

Nature, 2018, vol. 561, issue 7723, 343-348

Abstract: Abstract The naturally occurring channelrhodopsin variant anion channelrhodopsin-1 (ACR1), discovered in the cryptophyte algae Guillardia theta, exhibits large light-gated anion conductance and high anion selectivity when expressed in heterologous settings, properties that support its use as an optogenetic tool to inhibit neuronal firing with light. However, molecular insight into ACR1 is lacking owing to the absence of structural information underlying light-gated anion conductance. Here we present the crystal structure of G. theta ACR1 at 2.9 Å resolution. The structure reveals unusual architectural features that span the extracellular domain, retinal-binding pocket, Schiff-base region, and anion-conduction pathway. Together with electrophysiological and spectroscopic analyses, these findings reveal the fundamental molecular basis of naturally occurring light-gated anion conductance, and provide a framework for designing the next generation of optogenetic tools.

Keywords: Schiff Base Region; Retinal Binding Pocket (RBP); Anion Conductance Pathway; Optogenetic; Lipidic Cubic Phase (LCP) (search for similar items in EconPapers)
Date: 2018
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DOI: 10.1038/s41586-018-0511-6

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