Crystal structure of the natural anion-conducting channelrhodopsin GtACR1

Nature. 2018 Sep;561(7723):343-348. doi: 10.1038/s41586-018-0511-6. Epub 2018 Aug 29.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anions / metabolism*
  • Bacteriorhodopsins / chemistry
  • Binding Sites
  • Channelrhodopsins / chemistry*
  • Channelrhodopsins / metabolism*
  • Channelrhodopsins / radiation effects
  • Cryptophyta / chemistry*
  • Crystallography, X-Ray
  • Electric Conductivity
  • Ion Channel Gating / radiation effects
  • Ion Transport / radiation effects
  • Models, Molecular
  • Optogenetics / methods
  • Optogenetics / trends
  • Retinaldehyde / metabolism
  • Schiff Bases / chemistry


  • Anions
  • Channelrhodopsins
  • Schiff Bases
  • Bacteriorhodopsins
  • Retinaldehyde