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Crystal structure of the natural anion-conducting channelrhodopsin GtACR1

Author

Listed:
  • Yoon Seok Kim

    (and Howard Hughes Medical Institute, Stanford University)

  • Hideaki E. Kato

    (Stanford University School of Medicine
    Japan Science and Technology Agency, Honcho)

  • Keitaro Yamashita

    (RIKEN SPring-8 Center)

  • Shota Ito

    (Nagoya Institute of Technology)

  • Keiichi Inoue

    (Japan Science and Technology Agency, Honcho
    Nagoya Institute of Technology
    Nagoya Institute of Technology)

  • 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
    Stanford University)

  • Ron O. Dror

    (Stanford University
    Stanford University)

  • Hideki Kandori

    (Nagoya Institute of Technology
    Nagoya Institute of Technology)

  • Brian K. Kobilka

    (Stanford University School of Medicine)

  • Karl Deisseroth

    (and Howard Hughes Medical Institute, Stanford University)

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.

Suggested Citation

  • 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. Kobi, 2018. "Crystal structure of the natural anion-conducting channelrhodopsin GtACR1," Nature, Nature, vol. 561(7723), pages 343-348, September.
    • Handle: RePEc:nat:nature:v:561:y:2018:i:7723:d:10.1038_s41586-018-0511-6
    DOI: 10.1038/s41586-018-0511-6
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