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Structural mechanisms of selectivity and gating in anion channelrhodopsins

Author

Listed:
  • Hideaki E. Kato

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

  • Yoon Seok Kim

    (Stanford University
    Stanford University
    Stanford University)

  • Joseph M. Paggi

    (Stanford University
    Stanford University)

  • Kathryn E. Evans

    (Stanford University
    Stanford University
    Stanford University)

  • William E. Allen

    (Stanford University
    Stanford University
    Stanford University)

  • Claire Richardson

    (Stanford University)

  • Keiichi Inoue

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

  • Shota Ito

    (Nagoya Institute of Technology)

  • Charu Ramakrishnan

    (Stanford University
    Stanford University
    Stanford University)

  • Lief E. Fenno

    (Stanford University
    Stanford University
    Stanford University)

  • Keitaro Yamashita

    (RIKEN SPring-8 Center)

  • Daniel Hilger

    (Stanford University School of Medicine)

  • Soo Yeun Lee

    (Stanford University
    Stanford University
    Stanford University)

  • Andre Berndt

    (Stanford University
    Stanford University
    Stanford University)

  • Kang Shen

    (Stanford University
    Stanford University)

  • Hideki Kandori

    (Nagoya Institute of Technology
    Nagoya Institute of Technology)

  • Ron O. Dror

    (Stanford University
    Stanford University)

  • Brian K. Kobilka

    (Stanford University School of Medicine)

  • Karl Deisseroth

    (Stanford University
    Stanford University
    Stanford University)

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.

Suggested Citation

  • 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 & Danie, 2018. "Structural mechanisms of selectivity and gating in anion channelrhodopsins," Nature, Nature, vol. 561(7723), pages 349-354, September.
  • Handle: RePEc:nat:nature:v:561:y:2018:i:7723:d:10.1038_s41586-018-0504-5
    DOI: 10.1038/s41586-018-0504-5
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