Structural mechanisms of selectivity and gating in anion channelrhodopsins

Nature. 2018 Sep;561(7723):349-354. doi: 10.1038/s41586-018-0504-5. Epub 2018 Aug 29.


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.

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

  • Animals
  • Anions / metabolism*
  • Caenorhabditis elegans
  • Cells, Cultured
  • Channelrhodopsins / chemistry*
  • Channelrhodopsins / genetics
  • Channelrhodopsins / metabolism*
  • Channelrhodopsins / radiation effects
  • Crystallography, X-Ray
  • Electrophysiology
  • Female
  • HEK293 Cells
  • Hippocampus / cytology
  • Humans
  • Hydrogen-Ion Concentration
  • Ion Channel Gating* / radiation effects
  • Ion Transport / radiation effects
  • Kinetics
  • Male
  • Mice
  • Models, Molecular
  • Neurons / metabolism
  • Optogenetics / methods*
  • Substrate Specificity


  • Anions
  • Channelrhodopsins