Structural Characterization of pLGICs

As allosteric receptors, pentameric ligand-gated ion channels (pLGICs) participate in rapid electrochemical signal transduction in the nervous system by opening ion pores upon binding with neurotransmitters. Creative Bioarray focuses on providing clients with detailed structural characterization services of pLGICs, providing valuable information for studying the structural basis of channel allosteric transformation.

Introduction

pLGICs constitute a large family of neurotransduction receptor proteins, which play key roles in the rapid signal transduction throughout the nervous system. It is characterized by the formation of a pentamer structure by five heterologous or homologous subunits around the pseudosymmetricaxis perpendicular to the cell membrane. All subunits are composed of two different extracellular domain (ECD) and transmembrane domain (TMD). The ligand binding in the extracellular region can cause a conformational change in the channel to open the channel and allow cations to flow through the channel along the electrochemical gradient.

pLGICs are allosteric receptors, so analyzing the structural information of pLGICs in their liganded or ligand-free conformation is necessary to understand these complex molecular machines. Linking the determined structure with the canonical resting, open and desensitized states helps to fully describe their functions, providing a molecular basis for understanding the opening and closing (gating mechanism) of key players in the rapid transmission of chemical signals at synapses.

Fig. 1 Differential resolution of GLIC cryo-EM structures with varying pH. (Rovšnik, 2021)

Our Services

In the past decade, Creative Bioarray has made remarkable progress in the structural characterization of ion channels. We have established various techniques such as electrophysiology, X-ray crystallography, small-angle neutron scattering (SANS) and cryo-electron microscopy (cryo-EM) to help clients gain detailed new insights into the structure and function of prokaryotic and eukaryotic pLGICs. Our services include but not limited to:

• Analysis of structural information on the resting state of pGLICs at neutral pH.
• Structural characterization of pLGICs at varying pH.
• Analysis of Ca²⁺-bound closed-pore structure.
• Electrophysiology and crystallization analysis of pGLICs in the absence of Ca²⁺.
• Analysis of allosteric transitions and potential coupling in TMD and ligand-binding domain (LBD) sites.
• Structural characterization of allosteric potentiator binding.

We also provide specific characterization of different pGLIC members.

• Characterization of Glycine Receptor Chloride Channels
• Characterization of Nicotinic Acetylcholine Receptors
• Characterization of 5-HT₃ Receptors
• Characterization of GABA_A Receptor Ion Channels

Our characterization service is not limited to the characterization of structures, but also includes the following:

• Analysis of pLGIC-Lipid Interactions
• MD Simulation of Conformational Changes of pLGICs
• Pharmacological Analysis of pLGICs

Applications

Our pLGICs structural characterization service can be applied to the following research:

• Research on the function of pGLICs
• Analysis of intrinsic differences of different pGLICs activation mechanisms
• Research on the role and diversity of accessory domain interactions

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. Rovšnik, U.; et al. Dynamic closed states of a ligand-gated ion channel captured by cryo-EM and simulations. Life Science Alliance, 2021, 4(8).