Orthogonal optical control of a G protein-coupled receptor with a SNAP-tethered photochromic ligand

Johannes Broichhagen, Arunas Damijonaitis, Joshua Levitz, Kevin R. Sokol, Philipp Leippe, David Konrad, Ehud Y. Isacoff, Dirk Trauner

Research output: Contribution to journalArticlepeer-review


The covalent attachment of synthetic photoswitches is a general approach to impart light sensitivity onto native receptors. It mimics the logic of natural photoreceptors and significantly expands the reach of optogenetics. Here we describe a novel photoswitch design-the photos-witchable orthogonal remotely tethered ligand (PORTL)-that combines the genetically encoded SNAP-tag with photochromic ligands connected to a benzylguanine via a long flexible linker. We use the method to convert the G protein-coupled receptor mGluR2, a metabotropic glutamate receptor, into a photoreceptor (SNAG-mGluR2) that provides efficient optical control over the neuronal functions of mGluR2: presynaptic inhibition and control of excitability. The PORTL approach enables multiplexed optical control of different native receptors using distinct bioconjugation methods. It should be broadly applicable since SNAP-tags have proven to be reliable, many SNAP-tagged receptors are already available, and photochromic ligands on a long leash are readily designed and synthesized.

Original languageEnglish (US)
Pages (from-to)383-393
Number of pages11
JournalACS Central Science
Issue number7
StatePublished - Oct 28 2015

ASJC Scopus subject areas

  • General Chemistry
  • General Chemical Engineering


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