Structure-function analysis suggests that the photoreceptor LITE-1 is a light-activated ion channel

Curr Biol. 2023 Aug 21;33(16):3423-3435.e5. doi: 10.1016/j.cub.2023.07.008. Epub 2023 Jul 31.

Abstract

Sensation of light is essential for all organisms. The eye-less nematode Caenorhabditis elegans detects UV and blue light to evoke escape behavior. The photosensor LITE-1 absorbs UV photons with an unusually high extinction coefficient, involving essential tryptophans. Here, we modeled the structure and dynamics of LITE-1 using AlphaFold2-multimer and molecular dynamics (MD) simulations and performed mutational and behavioral assays in C. elegans to characterize its function. LITE-1 resembles olfactory and gustatory receptors from insects, recently shown to be tetrameric ion channels. We identified residues required for channel gating, light absorption, and mechanisms of photo-oxidation, involving a likely binding site for the peroxiredoxin PRDX-2. Furthermore, we identified the binding pocket for a putative chromophore. Several residues lining this pocket have previously been established as essential for LITE-1 function. A newly identified critical cysteine pointing into the pocket represents a likely chromophore attachment site. We derived a model for how photon absorption, via a network of tryptophans and other aromatic amino acids, induces an excited state that is transferred to the chromophore. This evokes conformational changes in the protein, possibly leading to a state receptive to oxidation of cysteines and, jointly, to channel gating. Electrophysiological data support the idea that LITE-1 is a photon and H2O2-coincidence detector. Other proteins with similarity to LITE-1, specifically C. elegans GUR-3, likely use a similar mechanism for photon detection. Thus, a common protein fold and assembly, used for chemoreception in insects, possibly by binding of a particular compound, may have evolved into a light-activated ion channel.

Keywords: AlphaFold2; Caenorhabditis elegans; UV-sensor; chromophore; gustatory receptor; hydrogen peroxide; ion channel; molecular dynamics simulation; nociceptor; photosensor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans Proteins* / genetics
  • Caenorhabditis elegans Proteins* / metabolism
  • Caenorhabditis elegans* / metabolism
  • Hydrogen Peroxide
  • Ion Channels / metabolism
  • Peroxiredoxins / metabolism
  • Receptors, Cell Surface / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • Hydrogen Peroxide
  • Ion Channels
  • Peroxiredoxins
  • PRDX-2 protein, C elegans
  • Receptors, Cell Surface
  • lite-1 protein, C elegans