Analysis of pLGIC-Lipid Interactions

Creative Bioarray is committed to revealing the structure of pLGICs at a higher resolution to help clients fully understand the interactions of lipids with pLGICs. The structural data we provide, combined with the analysis of lipid effects on pLGIC function, will greatly accelerate the study of the underlying mechanisms of pLGIC-lipid interactions and the implications of such interactions in human biology.

Introduction

In humans, the pLGIC superfamily plays a central role in synaptic communication. It has four families, including inhibitory anion selective pLGICs, such as γ-aminobutyric acid receptor type A receptor (GABB_A-R) and glycine receptor (Gly-R), as well as excitatory cation selective pLGICs, such as nicotinic acetylcholine receptor (nAChR) and serotonin receptor (5HT₃-R). The abnormality of these proteins often leads to a variety of neurological diseases, so pLGICs are considered to be important targets for the treatment of a variety of neuromuscular and neurological diseases.

pLGICs respond to the binding of neurotransmitters by opening ion channels instantaneously across presynaptic, postsynaptic, and nonsynaptic membranes. Studies have shown that lipids and other endogenous lipophilic molecules may participate in pLGICs mediated signaling and regulate the function of pLGICs. At present, characterization of the high-resolution structure of pLGICs has revealed information about the site of membrane lipid binding to pLGICs, providing a structural basis for exploring the mechanism of pLGIC-lipid interactions.

Fig. 1 Illustration of cholesterol binding to the α3β4 and α4β2 nAChR. (Thompson, 2020)

Our Services

We help our clients obtain lipid-binding sites of pLGICs through multiple techniques such as cryo-electron microscopy and X-ray crystallography to analyze lipid-pLGIC interactions and the functional impact of lipids on pLGIC functions. The services we provide include but not limited to:

• Analysis of nAChR-lipid interactions and functional sensitivity of nAChRs to lipids.
• Analysis of HT₃R-lipid interactions and characterization of bound lipids in 5HT₃R structures.
• Analysis of GABA_AR-lipid interactions and characterization of bound lipids in GABA_AR structures.
• Analysis of GlyR-lipid interactions and the effects of different lipids on GlyR function, and characterization of bound lipids in GlyR structures.
• Analysis of non-vertebrate pLGIC-lipid interactions, including lipids and GLIC, ELIC and the glutamate-activated chloride channel (GluCl).
• Prediction of cholesterol sites on nAChR and GABA_AR by combining structural templates and computational methods.

Applications

Our scientific services can help clients compare lipid binding to different pLGICs, providing insight into the general mechanisms of pLGIC-lipid interactions.

• Research on mechanisms underlying nAChR-lipid interactions
• Research on mechanisms underlying 5-HT₃R-lipid interactions
• Research on mechanisms underlying GABA_AR-lipid interactions
• Research on mechanisms of lipid action

Creative Bioarray is committed to developing a variety of technologies to help clients obtain detailed information about pLGICs in different physiologically related conformational states. We have the strength to provide our clients with unambiguous conformational insight, which is crucial for understanding the structure of pLGIC functions. If you are interested in our services, please contact us for more details.

Reference

1. Thompson, M. J.; Baenziger, J. E. Structural basis for the modulation of pentameric ligand-gated ion channel function by lipids. Biochimica et Biophysica Acta (BBA)-Biomembranes, 2020, 1862(9): 183304.