Structural Research of Cys-Loop Receptor Family

Ligand-gated ion channels (LGICs) of the Cys-loop receptor family are composed of nicotinic acetylcholine, GABAA, GABAA-ρ, glycine, 5-HT3 receptors, and zinc-activated (ZAC) receptors. These ion channels are involved in neurotransmission and are targets for many drugs, including anesthetics, sedatives, and muscle relaxants. These receptors are pentameric, meaning they consist of five protein subunits that form a pentameric arrangement around a central pore.

In recent years, there has been significant progress in the structural research of the Cys-loop receptor family. Researchers have utilized a variety of techniques, including X-ray crystallography, cryo-electron microscopy (cryo-EM), and molecular dynamics simulations, to better understand the receptor's structure and function. X-ray crystallography has been used to determine the structures of acetylcholine receptor and the glycine receptor. These structures have provided insights into the architecture of the receptor, including the arrangement of subunits and the location of key amino acid residues involved in ligand binding and channel gating. The cryo-EM technique has enabled researchers to study the receptor in different conformations and to visualize the dynamics of the receptor's movement during ion channel gating. Molecular dynamics simulations have been used to study the behavior of these proteins in lipid bilayers and to provide insights into the receptor's interaction with its environment. These simulations have also been used to predict the effect of mutations on the receptor's function and to design novel ligands that can target specific regions of the receptor.

Figure 1. Landscape of differential GABAA receptor assemblies. (Sente A, et al., 2022)

Table 1. Structural Research of Cys-Loop Receptor Family.

At Creative Biostructure, we take great pride in offering a comprehensive suite of cutting-edge protein structural analysis services that can aid in the research of the Cys-loop receptor family. Our X-ray crystallography services can determine the high-resolution structure of the receptor, while our cryo-EM services can provide structures of the receptor in different conformations.

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References

1. Rahman M M, et al. Structure of the native muscle-type nicotinic receptor and inhibition by snake venom toxins. Neuron. 2020, 106(6): 952-962. e5.
2. Zhang Y, et al. Asymmetric opening of the homopentameric 5-HT3A serotonin receptor in lipid bilayers. Nature Communications. 2021, 12(1): 1074.
3. Sente A, et al. Differential assembly diversifies GABAA receptor structures and signalling. Nature. 2022, 604(7904): 190-194.