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  SNAP-tagged nanobodies enable reversible optical control of a G protein-coupled receptor via a remotely tethered photoswitchable ligand

Farrants, H., Gutzeit, V. A., Ruiz, A. A., Trauner, D., Johnsson, K., Levitz, J., et al. (2018). SNAP-tagged nanobodies enable reversible optical control of a G protein-coupled receptor via a remotely tethered photoswitchable ligand. ACS Chemical Biology, 13(9), 2682-2688. doi:10.1021/acschembio.8b00628.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0001-FD42-8 Version Permalink: http://hdl.handle.net/21.11116/0000-0002-6C58-3
Genre: Journal Article
Abbreviation : Nanobody-mediated optical manipulation of a transmembrane receptor

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ACSChemBiol_13_2018_2682.pdf (Any fulltext), 3MB
 
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 Creators:
Farrants, Helen1, Author              
Gutzeit, Vanessa A., Author
Ruiz, Amanda Acosta, Author
Trauner, Dirk, Author
Johnsson, Kai1, Author              
Levitz, Joshua, Author
Broichhagen, Johannes1, Author              
Affiliations:
1Chemical Biology, Max Planck Institute for Medical Research, Max Planck Society, ou_2364732              

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 Abstract: G protein-coupled receptors (GPCRs) mediate the transduction of extracellular signals into complex intracellular responses. Despite their ubiquitous roles in physiological processes and as drug targets for a wide range of disorders, the precise mechanisms of GPCR function at the molecular, cellular, and systems levels remain partially understood. In order to dissect the function of individual receptors subtypes with high spatiotemporal precision, various optogenetic and photopharmacological approaches have been reported that use the power of light for receptor activation and deactivation. Here, we introduce a novel and, to date, most remote way of applying photoswitchable orthogonally remotely-tethered ligands (PORTLs) by using a SNAP-tag fused nanobody. Our nanobody-photoswitch conjugates (NPCs) can be used to target a GFP-fused metabotropic glutamate receptor by either gene-free application of purified complexes or co-expression of genetically encoded nanobodies to yield robust, reversible control of agonist binding and subsequent downstream activation. By harboring and combining the selectivity and flexibility of both nanobodies and self-labelling enzymes, we set the stage for targeting endogenous receptors in vivo.

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Language(s): eng - English
 Dates: 2018-07-042018-08-242018-08-242018-08-24
 Publication Status: Published in print
 Pages: 7
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1021/acschembio.8b00628
 Degree: -

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Title: ACS Chemical Biology
Source Genre: Journal
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Publ. Info: Washington, D.C. : American Chemical Society
Pages: - Volume / Issue: 13 (9) Sequence Number: - Start / End Page: 2682 - 2688 Identifier: ISSN: 1554-8929
CoNE: /journals/resource/1000000000035040