Characterization of GABA_A Receptor Ion Channels

Creative Bioarray is committed to providing clients with comprehensive type A γ-aminobutyric acid receptors (GABA_ARs) characterization services, including structural, functional, binding site, and kinetic analysis. Our specialized ion channel analysis services help clients gain new insights into the structural dynamics underlying GABA_AR function and modulation, providing valuable information to understand the pathogenesis of GABA_AR-related neurological and mental diseases.

Introduction

GABA_ARs are structurally pentameric-gated chloride channels that play an important role in the rapid inhibitory signaling in neural circuits. This signal process is regulated by basic drugs such as general anesthetics and benzodiazepines. GABA_ARs are widely distributed in the mammalian nervous system, suggesting that they have key physiological functions and the importance of being targets of therapeutic agents. Due to the complexity of the GABA_AR field, further work is needed to be carried out in different areas.

Exogenous ligands can interact with GABA_ARs at various sites to allosterically modify receptor function. However, many GABA_ARs binding sites remain unresolved, which makes it challenging to connect the binding of allosteric ligands to receptors with the activation of ion channels. In addition, although the different subunits that make up the GABA_ARs are well characterized in terms of expression levels and localization in a neuron, it is unclear which subunits collaborate to form a pentameric receptor and the subunit composition and arrangement. Therefore, it is necessary to further understand the structure, function, and regulation of GABA_ARs.

Fig. 1 Ten small ligand binding sites are found in atomic structures of GABA_A receptor homologs. (Puthenkalam, 2016)

Our Services

We help our clients characterize the structure and function of GABA_ARs and analyze the dynamic structure mechanism by combing a variety of technologies, including specific-site fluorescence technology, photochemical technology, computer simulation, electrophysiology, molecular biology, and other methods. Our services include but not limited to:

• Cellular localization and subcellular localization of GABA_ARs.
• Structural characterization of GABA_ARs.
• Model generation, such as the structural model of the N-terminal domain and transmembrane domain (TMD).
• Structural analysis of GABA_AR binding sites. We provide the mapping and assessment of binding sites in GABA_AR models, including the following:
• Multiple ligand binding sites at the extracellular domain (ECD) interface.
• Extracellular Intrasubunit sites 4-6.
• TMD inter-subunit and intra-subunit sites near the junction with the ECD.
• Lipid and putative steroid sites in the TMD.
• Structural dynamics analysis of GABA_ARs. We have established multiple new technologies, including site-specific fluorescence, luminescence resonance energy transfer (LRET), and photo crosslinking, to help our clients study the structural dynamics of GABA_ARs.
• Monitoring GABA-induced conformational changes.
• Measuring the distance changes between two residues at different sites of the receptor during channel activation.
• Evaluating the functional significance of the movement of specific amino acid residues in receptors.

Creative Bioarray has the strength to provide high-quality GABA_AR characterization services and to submit scientific and comprehensive experimental data for clients that are critical to understanding the mechanism of action for compounds with GABA_ARs as their major targets. These insights will also promote the development of new treatments for many neurological and psychiatric disorders. If you are interested in our services, please contact us for more details.

Reference

1. Puthenkalam, R.; et al. Structural studies of GABA_A receptor binding sites: which experimental structure tells us what?. Frontiers in molecular neuroscience, 2016, 9: 44.