Characterization of Glutamate Receptor Ion Channels

Creative Bioarray is committed to providing clients with structural characterization services of glutamate receptor ion channels through a variety of techniques such as X-ray crystallography and cryo-electron microscopy. Our advanced technology platform and extensive expertise ensure delivery of detailed and high-quality data on structures of glutamate receptor ion channels for our clients.

Introduction

Glutamate receptors are divided into two categories, one is metabotropic receptors (mGluRs), the other is ionotropic glutamate receptors (iGluRs), including three main subtypes (AMPA, kainic acid (KA) and NMDA receptors), which couple to ion channels to form receptor-channel complexes that mediate most of the excitatory neurotransmission in the central nervous system. Different glutamate receptor subunits exhibit different kinetic and pharmacological properties, but the sequence similarity between them suggests that they share common structural features.

Glutamate receptor subunits contain four discrete semiautonomous domains: the amino-terminal domain (ATD), the extracellular ligand-binding domain (LBD), the transmembrane domain (TMD), and the cytoplasmic carboxy-terminal domain ( CTD). Advances in crystallography and cryo-electron microscopy have now greatly accelerated progress in the structural biology of iGluRs, including the determination of numerous structures of isolated water-soluble ligand-binding and amino-terminal domains, and providing the possibility to visualize the conformational changes of the whole receptor, which greatly improved our understanding of iGluR gating mechanism.

Fig. 1 iGluR structural architecture and domain arrangement. (Twomey, 2018)

Our Services

We provide our clients with detailed structural characterization services of iGluRs. We not only help clients describe the structure of iGluRs in the non-ligand and resting state, but also help them analyze the closed and antagonist binding state of iGluRs. Our services include but not limited to:

• Structural characterization of tetrameric ionotropic glutamate receptor subtypes, including AMPA receptors, kainate receptors, NMDA receptors and CLUD receptors.
• Structural characterization of the extracellular agonist binding domains (ABD) of different ionotropic glutamate receptor subtypes.
• Structural characterization of the extracellular N-terminal domains (NTD) of iGluRs.
• Structural characterization of the extracellular TMD of iGluRs, including the pore domain or ion channel core, the membrane M2 re-entrant pore loop,and the transmembrane M4 helix and receptor assembly.

In addition to structural characterization, we also provide the following services：

• Functional Characterization of Glutamate Receptor Ion Channels.
• Kinetic Modeling of Glutamate Receptor Ion Channels.

Applications

The structural data we provide, combined with electrophysiology, biochemical experiments, molecular dynamics simulation and other technologies, can greatly accelerate the research on iGluR related fields, including:

• Structural visualization of iGluR gating mechanism
• Research on synapses physiology
• Drug design for iGluR in neurological diseases

Creative Bioarray focuses on the structural biology of iGluRs to provide our clients with more structural information about iGluRs as much as possible and accelerate the understanding of the assembly, activation and desensitization processes of iGluRs. If you are interested in our services, please contact us for more details.

Reference

1. Twomey, E. C.; Sobolevsky, A. I. Structural mechanisms of gating in ionotropic glutamate receptors. Biochemistry, 2018, 57(3): 267-276.