Crystal structure of a natural light-gated anion channelrhodopsin

Elife. 2019 Jan 7;8:e41741. doi: 10.7554/eLife.41741.

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.

Keywords: Guillardia theta; anion channelrhodopsin; biochemistry; chemical biology; molecular biophysics; optogenetics; structural biology.

Publication types

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

MeSH terms

  • Anions / chemistry
  • Channelrhodopsins / chemistry
  • Channelrhodopsins / metabolism*
  • Cryptophyta / metabolism*
  • Crystallography, X-Ray
  • Ion Channel Gating / physiology
  • Ion Transport
  • Optogenetics / methods
  • Retinoids / chemistry
  • Retinoids / metabolism*
  • Schiff Bases / chemistry
  • Schiff Bases / metabolism

Substances

  • Anions
  • Channelrhodopsins
  • Retinoids
  • Schiff Bases
  • retinylidene chromophore