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Updated: Mar 17, 2026

Using an α-Bungarotoxin Binding Site Tag to Study GABA A Receptor Membrane Localization and Trafficking
Published on: March 28, 2014
Side chain flexibility and the pore dimensions in the GABAA receptor
Alexey V Rossokhin1, Boris S Zhorov2,3
1Research Center of Neurology, RAS, by-str. Obukha 5, Moscow, Russia, 105064. alrossokhin@yahoo.com.
Abstract:
Permeation of ions through open channels and their accessibility to pore-targeting drugs depend on the pore cross-sectional dimensions, which are known only for static X-ray and cryo-EM structures. Here, we have built homology models of the closed, open and desensitized α1β2γ2 GABAA receptor (GABAAR). The models are based, respectively, on the X-ray structure of α3 glycine receptor (α3 GlyR), cryo-EM structure of α1 GlyR and X-ray structure of β3 GABAAR. We employed Monte Carlo energy minimizations to explore how the pore lumen may increase due to repulsions of flexible side chains from a variable-diameter electroneutral atom (an expanding sphere) pulled through the pore. The expanding sphere computations predicted that the pore diameter averaged along the permeation pathway is larger by approximately 3 Å than that computed for the models with fixed sidechains. Our models predict three major pore constrictions located at the levels of -2', 9' and 20' residues. Residues around the -2' and 9' rings are known to form the desensitization and activation gates of GABAAR. Our computations predict that the 20' ring may also serve as GABAAR gate whose physiological role is unclear. The side chain flexibility of residues -2', 9' and 20' and hence the dimensions of the constrictions depend on the GABAAR functional state.
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