Interfacial binding sites for cholesterol on GABA_A receptors and competition with neurosteroids.

ABSTRACT: γ-Aminobutyric acid type A (GABA_A) receptors in the brain are located in the outer membranes of brain cells where the concentration of cholesterol is high. Of the 25 available high-resolution structures available for GABA_A receptors, none were determined in the presence of cholesterol, but four include resolved molecules of cholesterol hemisuccinate (CHS). Here, a molecular docking procedure is used to sweep the transmembrane (TM) surfaces of the receptors for cholesterol binding sites. Cholesterol docking poses determined in this way match 89% of the resolved CHS when CHS molecules deemed unlikely to represent typical bound cholesterols are excluded. The receptors are pentameric, and their TM surfaces consist of a set of five facets, each including pairs of TM helice

SUBMITTER: Lee AG 

PROVIDER: S-EPMC8390853 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature