Modulation of α1β3γ2 GABA_A receptors expressed in X. laevis oocytes using a propofol photoswitch tethered to the transmembrane helix.

ABSTRACT: Tethered photoswitches are molecules with two photo-dependent isomeric forms, each with different actions on their biological targets. They include reactive chemical groups capable of covalently binding to their target. Our aim was to develop a β-subunit-tethered propofol photoswitch (MAP20), as a tool to better study the mechanism of anesthesia through the GABA_A α1β3γ2 receptor. We used short spacers between the tether (methanethiosulfonate), the photosensitive moiety (azobenzene), and the ligand (propofol), to allow a precise tethering adjacent to the putative propofol binding site at the β⁺α^- interface of the receptor transmembrane helices (TMs). First, we used molecular modeling to identify possible tethering sites in β3TM3 and α1TM1, and then introduce

SUBMITTER: Borghese CM 

PROVIDER: S-EPMC7923644 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature