Molecular analysis of the site for 2-arachidonylglycerol (2-AG) on the β 2 subunit of GABA A receptors

Baur, Roland; Kielar, Marie; Richter, Lars; Ernst, Margot; Ecker, Gerhard F.; Sigel, Erwin (2013). Molecular analysis of the site for 2-arachidonylglycerol (2-AG) on the β 2 subunit of GABA A receptors. Journal of neurochemistry, 126(1), pp. 29-36. Wiley-Blackwell 10.1111/jnc.12270

Full text not available from this repository. (Request a copy)

2-arachidonyl glycerol (2-AG) allosterically potentiates GABAA receptors via a binding site located in transmembrane segment M4 of the β2 subunit. Two amino acid residues have been described that are essential for this effect. With the aim to further describe this potential drug target, we performed a cysteine scanning of the entire M4 and part of M3. All four residues in M4 affecting the potentiation here and the two already identified residues locate to the same side of the α-helix. This side is exposed to M3, where further residues were identified. From the fact that the important residues span > 18 Å, we conclude that the hydrophobic tail of the bound 2-AG molecule must be near linear and that the site mainly locates to the inner leaflet but stretches far into the membrane. The influence of the structure of the head group of the ligand molecule on the activity of the molecule was also investigated. We present a model of 2-AG docked to the GABAA receptor.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine

UniBE Contributor:

Baur, Roland; Kielar, Marie and Sigel, Erwin

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0022-3042

Publisher:

Wiley-Blackwell

Language:

English

Submitter:

Erwin Sigel

Date Deposited:

17 Apr 2014 09:22

Last Modified:

17 Apr 2014 09:22

Publisher DOI:

10.1111/jnc.12270

Uncontrolled Keywords:

2-arachidonylglycerol (2-AG), endocannabinoids, GABA , GABAA receptors

URI:

https://boris.unibe.ch/id/eprint/39563

Actions (login required)

Edit item Edit item
Provide Feedback