Baur, Roland; Lüscher, Benjamin P; Richter, Lars; Sigel, Erwin (2010). A residue close to ?1 loop F disrupts modulation of GABAA receptors by benzodiazepines while their binding is maintained. Journal of neurochemistry, 115(6), pp. 1478-85. Oxford: Wiley-Blackwell 10.1111/j.1471-4159.2010.07052.x
Full text not available from this repository.Benzodiazepines act at the major isoforms of GABA type A receptors where they potentiate the current evoked by the agonist GABA. The underlying mechanism of this potentiation is poorly understood, but hypothesized to be related to the mechanism that links agonist binding to channel opening in these ligand activated ion channels. The loop F of the ?(1) and the ?(2) subunit have been implicated in channel gating, and loop F of the ?(2) subunit in the modulation by benzodiazepines. We have identified the conservative point mutation Y168F located N-terminally of loop F in the ?(1) subunit that fails to affect agonist properties. Interestingly, it disrupts modulation by benzodiazepines, but leaves high affinity binding to the benzodiazepine binding site intact. Modulation by barbiturates and neurosteroids is also unaffected. Residue ?(1) Y168 is not located either near the binding pockets for GABA, or for benzodiazepines, or close to the loop F of the ?(2) subunit. Our results support the fact, that broader regions of ligand gated receptors are conformationally affected by the binding of benzodiazepines. We infer that also broader regions could contribute to signaling from GABA agonist binding to channel opening.
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, Sigel, Erwin |
ISSN: |
0022-3042 |
Publisher: |
Wiley-Blackwell |
Language: |
English |
Submitter: |
Factscience Import |
Date Deposited: |
04 Oct 2013 14:12 |
Last Modified: |
05 Dec 2022 14:01 |
Publisher DOI: |
10.1111/j.1471-4159.2010.07052.x |
PubMed ID: |
20946417 |
Web of Science ID: |
000284852600016 |
URI: |
https://boris.unibe.ch/id/eprint/2426 (FactScience: 204924) |
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