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A propofol binding site on mammalian GABAA receptors identified by photolabeling.

Abstract：

:Propofol is the most important intravenous general anesthetic in current clinical use. It acts by potentiating GABAA (γ-aminobutyric acid type A) receptors, but where it binds to this receptor is not known and has been a matter of some debate. We synthesized a new propofol analog photolabeling reagent whose biological activity is very similar to that of propofol. We confirmed that this reagent labeled known propofol binding sites in human serum albumin that have been identified using X-ray crystallography. Using a combination of protiated and deuterated versions of the reagent to label mammalian receptors in intact membranes, we identified a new binding site for propofol in GABAA receptors consisting of both β3 homopentamers and α1β3 heteropentamers. The binding site is located within the β subunit at the interface between the transmembrane domains and the extracellular domain and lies close to known determinants of anesthetic sensitivity in the transmembrane segments TM1 and TM2.

journal_name

Nat Chem Biol

journal_title

Nature chemical biology

authors

Yip GM,Chen ZW,Edge CJ,Smith EH,Dickinson R,Hohenester E,Townsend RR,Fuchs K,Sieghart W,Evers AS,Franks NP

doi

10.1038/nchembio.1340

subject

Has Abstract

pub_date

2013-11-01 00:00:00

pages

715-20

issue

11

eissn

1552-4450

issn

1552-4469

pii

nchembio.1340

journal_volume

9

pub_type

杂志文章

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