Crystal structure of a natural light-gated anion channelrhodopsin

Hai Li, Chia Ying Huang, Elena G Govorunova, Christopher T. Schafer, Oleg A. Sineshchekov, Meitian Wang, Lei Zheng, John L Spudich

Research output: Contribution to journalArticle

Abstract

The anion channelrhodopsin GtACR1 from the alga Guillardia theta is a potent neuron-inhibiting optogenetics tool. Presented here, its X-ray structure at 2.9 Å reveals a tunnel traversing the protein from its extracellular surface to a large cytoplasmic cavity. The tunnel is lined primarily by small polar and aliphatic residues essential for anion conductance. A disulfide-immobilized extracellular cap facilitates channel closing and the ion path is blocked mid-membrane by its photoactive retinylidene chromophore and further by a cytoplasmic side constriction. The structure also reveals a novel photoactive site configuration that maintains the retinylidene Schiff base protonated when the channel is open. These findings suggest a new channelrhodopsin mechanism, in which the Schiff base not only controls gating, but also serves as a direct mediator for anion flux.

LanguageEnglish
JournaleLife
Volume8
DOIs
StatePublished - Jan 7 2019

Fingerprint

Anions
Schiff Bases
Crystal structure
Light
Tunnels
Optogenetics
Algae
Ion Channels
Constriction
Disulfides
Neurons
X-Rays
Ions
Fluxes
Membranes
X rays
Proteins
retinylidene chromophore

Keywords

  • anion channelrhodopsin
  • biochemistry
  • chemical biology
  • Guillardia theta
  • molecular biophysics
  • optogenetics
  • structural biology

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Li, H., Huang, C. Y., Govorunova, E. G., Schafer, C. T., Sineshchekov, O. A., Wang, M., ... Spudich, J. L. (2019). Crystal structure of a natural light-gated anion channelrhodopsin. eLife, 8. https://doi.org/10.7554/eLife.41741

Crystal structure of a natural light-gated anion channelrhodopsin. / Li, Hai; Huang, Chia Ying; Govorunova, Elena G; Schafer, Christopher T.; Sineshchekov, Oleg A.; Wang, Meitian; Zheng, Lei; Spudich, John L.

In: eLife, Vol. 8, 07.01.2019.

Research output: Contribution to journalArticle

Li, H, Huang, CY, Govorunova, EG, Schafer, CT, Sineshchekov, OA, Wang, M, Zheng, L & Spudich, JL 2019, 'Crystal structure of a natural light-gated anion channelrhodopsin', eLife, vol. 8. https://doi.org/10.7554/eLife.41741
Li H, Huang CY, Govorunova EG, Schafer CT, Sineshchekov OA, Wang M et al. Crystal structure of a natural light-gated anion channelrhodopsin. eLife. 2019 Jan 7;8. https://doi.org/10.7554/eLife.41741
Li, Hai ; Huang, Chia Ying ; Govorunova, Elena G ; Schafer, Christopher T. ; Sineshchekov, Oleg A. ; Wang, Meitian ; Zheng, Lei ; Spudich, John L. / Crystal structure of a natural light-gated anion channelrhodopsin. In: eLife. 2019 ; Vol. 8.
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