Recombinant Human Glycine receptor subunit alpha-1 (GLRA1), partial

1. Results support the notion that the efficacies of ligands for the alpha1 GlyR are determined by conformational changes that occur within and near the ligand-binding domain: disruption of the D97-R119 interaction may be an important element in receptor activation and that agonists may break this putative intersubunit bond in order to destabilize the initial shut state and facilitate transitions towards the open state. PMID: 27923639
2. The E103K startle mutation reduces the sensitivity of glycine receptor alpha 1 to both glycine and sarcosine and impairs channel gating. PMID: 28174298
3. gain-of-function GLRA1 mutations also cause hyperekplexia, although the mechanism is unknown. Here we identify two new gain-of-function mutations (I43F and W170S) and characterize these along with known gain-of-function mutations (Q226E, V280M, and R414H) to identify how they cause hyperekplexia. PMID: 27226610
4. GLRA1 and GLRB mutations are responsible for abnormal startled reactions in humans. (Review) PMID: 26845851
5. in two sisters with hyperekplexia a compound heterozygosis of 2 novel mutations of GLRA1 gene was found - heterozygous for a C-to-G base transition resulting in a phenylalanine to leucine amino acid change in position 235 and for a T-to-C base transition resulting in a cysteine to arginine amino acid change in position 237 PMID: 25079583
6. the TM3-4 loop length is critical for glycine receptor alpha1 desensitization and a direct neighborhood of both basic stretches changes receptor properties from non-desensitizing to desensitizing. PMID: 26079326
7. Self-declared ethnicity can predict gene-screening outcomes. Cultural practices influence the inheritance patterns and a Caucasian founder is postulated for R271 mutations. PMID: 24970905
8. Mutations in the GLRA1 were identified in 16 Japanese patients with hyperekplexia. PMID: 25356525
9. Data indicate that alpha1Q-26'E-containing glycine receptors have longer active periods and lower conductances. PMID: 25572390
10. The first X-ray structure of the TMD of the alpha1GlyR solved here using GLIC as a scaffold paves the way for mechanistic investigation and design of allosteric modulators of a human receptor. PMID: 25730860
11. In GlyRA1 mutants, a portion of them can be transported to the plasma membrane but don't form funtional channels; a possible cause for hyperekplexia. PMID: 25568133
12. Comparison of glycine-mediated conformational changes in the extracellular M2-M3 domain finds significantly different structures between GlyR alpha3 and GlyR alpha1 isoforms. PMID: 23834509
13. Conformation and function of the human GLRA1 chloride channel. PMID: 23994010
14. Analysis of hyperekplexia mutations identifies transmembrane domain rearrangements that mediate glycine receptor activation. PMID: 24097980
15. p.E375X truncated subunits are incorporated into functional hGlyRs together with unmutated alpha1 or alpha1 plus beta subunits. PMID: 24108130
16. Normal-mode analysis shows that a glycine alpha-1 receptor suspended in a fully hydrated lipid bilayer continues to demonstrate an iris-like channel gating motion as a low-frequency, high-amplitude natural harmonic vibration consistent with channel gating. PMID: 22816018
17. Glycine receptor alpha1 subunit specific-autoantibody study aids identification of autoimmune brainstem/spinal cord hyperexcitability disorders and may extend to the glycinergic visual system. PMID: 23090334
18. Ethanol mediated potentiation of GlyR is in part by Gbetagamma activation. PMID: 23035114
19. TM3-4 loop subdomains are important for functional reconstitution of glycine receptors by independent domains PMID: 22995908
20. A 12-amino-acid segment incorporating the 271 residue on the glycine receptor alpha1271Q/L subunit was replaced by the homologous segment from the glycine receptor beta subunit (alpha1(Ch) 271Q/L). The function of the alpha1(Ch) 271Q/L glycine receptor was examined. PMID: 21955162
21. a novel p.W170S mutation in the extracellular ligand binding domain of glycine receptor alpha1 subunit was detected in patients with hyperekplexia and mild mental retardation. PMID: 22264702
22. Mutations in the GlyR alpha-1 subunit, M287L and Q266I, resulted in a small but general impairment of glycine action, that is most evident in the glycine-induced maximal currents. PMID: 22037201
23. Hereditary hyperekplexia-causing mutations that modify alpha1 beta GlyR channel function are almost exclusively located in the alpha1 to the exclusion of the beta subunit. PMID: 22132222
24. By slowing and impairing channel gating in GLRA1, the K276E mutation facilitates the detection of closed reaction intermediates in the activation pathway of glycine channels. PMID: 22279218
25. Activation and desensitization induce distinct conformational changes at the extracellular-transmembrane domain interface of the glycine receptor PMID: 21917927
26. ethanol appears to stabilize the GlyR model built on a presumably open form of the ligand-gated channel. PMID: 21463577
27. Selective alterations in GlyRalpha1 subunit function contribute to inhibitory insufficiency in motoneurons early in the disease process of amyotrophic lateral sclerosis. PMID: 21414903
28. Depolarization of GlyCl-expressing cells induces these drastic changes in melanocyte behavior via a serotonin-transporter-dependent increase of extracellular serotonin PMID: 20959630
29. the coordination environment of Cu(2)(+) in the human alpha1-glycine receptor PMID: 20959090
30. sequencing of GLRA1 in 88 new unrelated hyperekplexia patients revealed 19 sequence variants in 30 index cases, of which 21 were inherited in recessive or compound heterozygote modes; investigated functional effects of 11 novel and 2 recurrent mutations PMID: 20631190
31. Presence of an impermeant Ca(2+) ion in the Glra1 channel pore region just external to the selectivity filter tends to electrostatically retard outward movement of Na(+) ions and to enhance movement of Cl(-) ions down their energy gradients. PMID: 20198385
32. Results indicate that the multifunctional basic motif of the TM3-4 loop is capable of mediating a karyopherin-dependent intracellular sorting of full-length GlyRs. PMID: 19959465
33. Sequencing analysis of all exons of the alpha1 subunit of the glycine receptor (GLRA1) gene revealed a G1158A base transition in affected, heterozygous patients. PMID: 11781706
34. A novel recessive hyperekplexia allele GLRA1 (S231R): genotyping by MALDI-TOF mass spectrometry and functional characterisation PMID: 11973623
35. A single substitution at the intracellular mouth of the alpha 1 glycine receptor M2 domain converts the channel charge selectivity to cations over anions, providing evidence of critical electrostatic interactions between permeating ions and pore residues. PMID: 11981020
36. Ion charge selectivity mutation of the alpha 1 homomeric glycine receptor inverts the electrostatic profile of the channel pore by introducing a negatively charged ring at the putative selectivity filter. PMID: 11981021
37. Probing the topology of the glycine receptor alpha1 by chemical modification coupled to mass spectrometry. PMID: 11994009
38. NMR of GLRA1 reveals a pore architecture in which simultaneous tilting movements of entire TM2 helices by a mere 10 degrees may be sufficient to account for the channel gating PMID: 12080117
39. variations in glycine receptor alpha1(GlyR) density during cluster formation result from a change in GlyR efficiency due to modifications in their desensitization properties. PMID: 12237328
40. Results provide evidence for a conserved pore opening mechanism in anion-selective members of the ligand-gated ion channel family, including glycine receptors (GlyR) and gamma-aminobutyric acid, type A receptors (GABA(A)R). PMID: 12239220
41. Effects of phosphorylation on glycine receptor kinetics. with phosphorylators or with phosphatases. Phosphorylation accelerated desensitisation, but slowed deactivation and recovery from desensitisation. PMID: 12356883
42. Treatment of the glycine receptor alpha 1 channel with ginsenoside Rf enhances glycine-induced inward peak current (IGly) in a dose dependent and reversible manner but ginsenoside Rf itself did not elicit membrane currents. PMID: 12661758
43. We propose a kinetic scheme with three independent open states, where the opening rates are dependent upon the activating agonist, while the closing rates are an intrinsic characteristic of the receptor. PMID: 12679369
44. binding of zinc at the interface between adjacent glycine receptor alpha1 subunits could restrict intersubunit movements, providing a feasible mechanism for the inhibition of channel activation by zinc PMID: 12740384
45. novel GLRA1 mutation, occurring de novo in a patient with hyperekplexia, which results in the substitution of the arginine at position 218 with a glutamine (R218Q) PMID: 12746425
46. findings indicate that pressure directly and selectively antagonizes ethanol potentiation of alpha(1)glycine receptor function PMID: 12766618
47. a highly conserved aspartic acid residue in the signature disulfide loop of the alpha 1 subunit is a determinant of gating in the glycine receptor PMID: 12826676
48. We produced knock-in mice bearing the human GlyR alpha1 S267Q dominant-negative point mutation in GlyR, disrupting normal function and producing a more dramatic phenotype than the corresponding recessive null mutation PMID: 12954867
49. loops 2 and 7 in the extracellular domain play an important role in the mechanism of activation of the glycine receptor although not by a direct electrostatic mechanism PMID: 14525990
50. proton modulation of glycine receptor function is determined by extracellular domain in both the alpha1 and beta subunits PMID: 14563849

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HGNC: 4326

OMIM: 138491

KEGG: hsa:2741

STRING: 9606.ENSP00000411593

UniGene: Hs.121490