Photoaffinity labeling identifies an intersubunit steroid-binding site in heteromeric GABA type A (GABA_A) receptors.

ABSTRACT: Allopregnanolone (3α5α-P), pregnanolone, and their synthetic derivatives are potent positive allosteric modulators (PAMs) of GABA_A receptors (GABA_ARs) with in vivo anesthetic, anxiolytic, and anti-convulsant effects. Mutational analysis, photoaffinity labeling, and structural studies have provided evidence for intersubunit and intrasubunit steroid-binding sites in the GABA_AR transmembrane domain, but revealed only little definition of their binding properties. Here, we identified steroid-binding sites in purified human α1β3 and α1β3γ2 GABA_ARs by photoaffinity labeling with [³H]21-[4-(3-(trifluoromethyl)-3H-diazirine-3-yl)benzoxy]allopregnanolone ([³H]21-pTFDBzox-AP), a potent GABA_AR PAM. Protein micr

SUBMITTER: Jayakar SS 

PROVIDER: S-EPMC7450100 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature