GLRA1 Membrane Protein Introduction

Introduction of GLRA1

Glycine receptor subunit alpha-1 (GLRA1), also known as Glycine receptor 48 kDa subunit or Glycine receptor strychnine-binding subunit, is a protein that in humans is encoded by the GLRA1 gene. Glycine receptors (GlyR) are members of the cys-loop family of ligand-gated ion channels, responsible for mediating the inhibitory effects of glycine. They are widely distributed throughout the CNS, particularly within the hippocampus, spinal cord, and brain stem. Most GlyR in adults is composed of α1β heteromers, but α1 subunits can also form functional homomeric receptors in many expression systems. Glycine is thought to be the endogenous ligand for synaptic GlyR, but evidence exists that taurine tonically activates extrasynaptic GlyR.

Function of GLRA1 Membrane Protein

Glycine receptors (GlyR) belong to the pentameric ligand-gated ion channel (pLGIC) superfamily and mediate fast inhibitory transmission in the vertebrate CNS. The disruption of glycinergic transmission through inherited mutations can cause panic disease in humans. Many startle mutations that are in GlyRs provide useful clues to the function of the channel domains. Glycine receptor subunit alpha-1 protein mediates postsynaptic inhibition in the CNS. Defects in the GLRA1 gene are a cause of startle disease, also known as congenital stiff-person syndrome or hereditary hyperekplexia. Multiple transcript variants encoding different isoforms have been found. Diseases associated with GLRA1 include Hyperekplexia, Hereditary 1 and Hyperekplexia. Among its related pathways are peptide ligand-binding receptors and DAG and IP3 signaling.

Fig.1 Structure of ligand-gated ion channels. (Haverkamp, 2012)

Application of GLRA1 Membrane Protein in Literature

1. Safar F., et al. The Startle Disease Mutation E103K Impairs Activation of Human Homomeric α1 Glycine Receptors by Disrupting an Intersubunit Salt Bridge across the Agonist Binding Site. J Biol Chem. 2017, 292(12): 5031-5042. PubMed ID: 28174298
   
   

   The study reveals that the startle disease mutation E103K impairs the activation of the human homomeric α1 glycine receptors by disrupting an intersubunit salt bridge across the agonist binding site.

2. Welsh B.T., et al. Disruption of a putative intersubunit electrostatic bond enhances agonist efficacy at the human α1 glycine receptor. Brain Res. 2017, 1657: 148-155. PubMed ID: 27923639
   
   

   The article reports that the determination of the efficacy following ligand binding to the glycine receptor may involve the disruption of an intersubunit electrostatic interaction occurring near the agonist binding site.

3. Zhang Y., et al. Investigating the Mechanism by Which Gain-of-function Mutations to the α1 Glycine Receptor Cause Hyperekplexia. J Biol Chem. 2016, 291(29): 15332-41. PubMed ID: 27226610
   
   

   The article indicates that perlecan binds the clustering molecule gliomedin and enhances clustering of a node of Ranvier components.

4. Moraga-Cid G., et al. Allosteric and hyperekplexic mutant phenotypes investigated on an α1 glycine receptor transmembrane structure. Proc Natl Acad Sci U S A. 2015, 112(9): 2865-70. PubMed ID: 25730860
   
   

   Authors in this group investigate the allosteric and hyperekplexic mutant phenotypes on an α1 glycine receptor transmembrane structure. The first X-ray structure of the TMD of the α1GlyR using GLIC as a scaffold paves the way for mechanistic studies and the design of allosteric modulators of human receptors.

5. Burgos C.F., et al. Evidence for α-helices in the large intracellular domain mediating modulation of the α1-glycine receptor by ethanol and Gβγ. J Pharmacol Exp Ther. 2015, 352(1): 148-55. PubMed ID: 25339760
   
   

   This article reports that α-helices in the large intracellular domain mediate modulation of the α1-glycine receptor by ethanol and Gβγ.

GLRA1 Preparation Options

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Reference

1. Haverkamp S, et al. (2012). Glycine Receptor Diversity in the Mammalian Retina. The Organization of the Retina and Visual System.

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