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 journalArticle

Abstract

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
Volume1
Issue number7
DOIs
StatePublished - Oct 28 2015

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G-Protein-Coupled Receptors
Ligands
Proteins
Metabotropic Glutamate Receptors
Photosensitivity
metabotropic glutamate receptor 2

ASJC Scopus subject areas

  • Chemical Engineering(all)
  • Chemistry(all)

Cite this

Broichhagen, J., Damijonaitis, A., Levitz, J., Sokol, K. R., Leippe, P., Konrad, D., ... Trauner, D. (2015). Orthogonal optical control of a G protein-coupled receptor with a SNAP-tethered photochromic ligand. ACS Central Science, 1(7), 383-393. https://doi.org/10.1021/acscentsci.5b00260

Orthogonal optical control of a G protein-coupled receptor with a SNAP-tethered photochromic ligand. / Broichhagen, Johannes; Damijonaitis, Arunas; Levitz, Joshua; Sokol, Kevin R.; Leippe, Philipp; Konrad, David; Isacoff, Ehud Y.; Trauner, Dirk.

In: ACS Central Science, Vol. 1, No. 7, 28.10.2015, p. 383-393.

Research output: Contribution to journalArticle

Broichhagen, J, Damijonaitis, A, Levitz, J, Sokol, KR, Leippe, P, Konrad, D, Isacoff, EY & Trauner, D 2015, 'Orthogonal optical control of a G protein-coupled receptor with a SNAP-tethered photochromic ligand', ACS Central Science, vol. 1, no. 7, pp. 383-393. https://doi.org/10.1021/acscentsci.5b00260
Broichhagen J, Damijonaitis A, Levitz J, Sokol KR, Leippe P, Konrad D et al. Orthogonal optical control of a G protein-coupled receptor with a SNAP-tethered photochromic ligand. ACS Central Science. 2015 Oct 28;1(7):383-393. https://doi.org/10.1021/acscentsci.5b00260
Broichhagen, Johannes ; Damijonaitis, Arunas ; Levitz, Joshua ; Sokol, Kevin R. ; Leippe, Philipp ; Konrad, David ; Isacoff, Ehud Y. ; Trauner, Dirk. / Orthogonal optical control of a G protein-coupled receptor with a SNAP-tethered photochromic ligand. In: ACS Central Science. 2015 ; Vol. 1, No. 7. pp. 383-393.
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