2m6b

From Proteopedia

(Difference between revisions)

Revision as of 09:29, 14 June 2023

Structure of full-length transmembrane domains of human glycine receptor alpha1 monomer subunit

Structural highlights

2m6b is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

GLRA1_HUMAN Defects in GLRA1 are the cause of hyperekplexia, hereditary, type 1 (HKPX1) [MIM:149400. A neurologic disorder characterized by muscular rigidity of central nervous system origin, particularly in the neonatal period, and by an exaggerated startle response to unexpected acoustic or tactile stimuli.^[1] [:]^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10]

Function

GLRA1_HUMAN The glycine receptor is a neurotransmitter-gated ion channel. Binding of glycine to its receptor increases the chloride conductance and thus produces hyperpolarization (inhibition of neuronal firing).

Publication Abstract from PubMed

Glycine receptors play a major role in mediating fast inhibitory neurotransmission in the spinal cord and brain stem, yet their high-resolution structures remain unsolved. We determined open-channel structures of the full-length transmembrane domain (TMD) of the human glycine receptor alpha1-subunit (hGlyR-alpha1) using nuclear magnetic resonance (NMR) spectroscopy and electron micrographs. hGlyR-alpha1 TMD spontaneously forms pentameric Cl--conducting channels, with structures sharing overall topology observed in crystal structures of homologous bacterial and nematode pentameric ligand-gated ion channels (pLGICs). However, the mammalian hGlyR-alpha1 structures present several distinctive features, including a shorter, pore-lining TM2 helix with helical unwinding near the C-terminal end, a TM3 helical kink at A288 that partially overlaps with the homologous ivermectin-binding site in GluCl, and a highly dynamic segment between S267(15') of TM2 and A288 that likely affects allosteric modulations of channel function. Our structures provide additional templates for identifying potential drug targets in GlyRs and other mammalian pLGICs.

Open-Channel Structures of the Human Glycine Receptor alpha1 Full-Length Transmembrane Domain.,Mowrey DD, Cui T, Jia Y, Ma D, Makhov AM, Zhang P, Tang P, Xu Y Structure. 2013 Aug 28. pii: S0969-2126(13)00264-5. doi:, 10.1016/j.str.2013.07.014. PMID:23994010^[11]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Shiang R, Ryan SG, Zhu YZ, Hahn AF, O'Connell P, Wasmuth JJ. Mutations in the alpha 1 subunit of the inhibitory glycine receptor cause the dominant neurologic disorder, hyperekplexia. Nat Genet. 1993 Dec;5(4):351-8. PMID:8298642 doi:http://dx.doi.org/10.1038/ng1293-351
↑ Langosch D, Laube B, Rundstrom N, Schmieden V, Bormann J, Betz H. Decreased agonist affinity and chloride conductance of mutant glycine receptors associated with human hereditary hyperekplexia. EMBO J. 1994 Sep 15;13(18):4223-8. PMID:7925268
↑ Schorderet DF, Pescia G, Bernasconi A, Regli F. An additional family with Startle disease and a G1192A mutation at the alpha 1 subunit of the inhibitory glycine receptor gene. Hum Mol Genet. 1994 Jul;3(7):1201. PMID:7981700
↑ Rees MI, Andrew M, Jawad S, Owen MJ. Evidence for recessive as well as dominant forms of startle disease (hyperekplexia) caused by mutations in the alpha 1 subunit of the inhibitory glycine receptor. Hum Mol Genet. 1994 Dec;3(12):2175-9. PMID:7881416
↑ Shiang R, Ryan SG, Zhu YZ, Fielder TJ, Allen RJ, Fryer A, Yamashita S, O'Connell P, Wasmuth JJ. Mutational analysis of familial and sporadic hyperekplexia. Ann Neurol. 1995 Jul;38(1):85-91. PMID:7611730 doi:http://dx.doi.org/10.1002/ana.410380115
↑ Milani N, Dalpra L, del Prete A, Zanini R, Larizza L. A novel mutation (Gln266-->His) in the alpha 1 subunit of the inhibitory glycine-receptor gene (GLRA1) in hereditary hyperekplexia. Am J Hum Genet. 1996 Feb;58(2):420-2. PMID:8571969
↑ Elmslie FV, Hutchings SM, Spencer V, Curtis A, Covanis T, Gardiner RM, Rees M. Analysis of GLRA1 in hereditary and sporadic hyperekplexia: a novel mutation in a family cosegregating for hyperekplexia and spastic paraparesis. J Med Genet. 1996 May;33(5):435-6. PMID:8733061
↑ Seri M, Bolino A, Galietta LJ, Lerone M, Silengo M, Romeo G. Startle disease in an Italian family by mutation (K276E): The alpha-subunit of the inhibiting glycine receptor. Hum Mutat. 1997;9(2):185-7. PMID:9067762 doi:<185::AID-HUMU14>3.0.CO;2-Z 10.1002/(SICI)1098-1004(1997)9:2<185::AID-HUMU14>3.0.CO;2-Z
↑ Vergouwe MN, Tijssen MA, Peters AC, Wielaard R, Frants RR. Hyperekplexia phenotype due to compound heterozygosity for GLRA1 gene mutations. Ann Neurol. 1999 Oct;46(4):634-8. PMID:10514101
↑ Saul B, Kuner T, Sobetzko D, Brune W, Hanefeld F, Meinck HM, Becker CM. Novel GLRA1 missense mutation (P250T) in dominant hyperekplexia defines an intracellular determinant of glycine receptor channel gating. J Neurosci. 1999 Feb 1;19(3):869-77. PMID:9920650
↑ Mowrey DD, Cui T, Jia Y, Ma D, Makhov AM, Zhang P, Tang P, Xu Y. Open-Channel Structures of the Human Glycine Receptor alpha1 Full-Length Transmembrane Domain. Structure. 2013 Aug 28. pii: S0969-2126(13)00264-5. doi:, 10.1016/j.str.2013.07.014. PMID:23994010 doi:10.1016/j.str.2013.07.014

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2m6b"

@@ Line 1: / Line 1: @@
 ==Structure of full-length transmembrane domains of human glycine receptor alpha1 monomer subunit==
-<StructureSection load='2m6b' size='340' side='right'caption='[[2m6b]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''>
+<StructureSection load='2m6b' size='340' side='right'caption='[[2m6b]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2m6b]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M6B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M6B FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2m6b]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M6B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M6B FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2m6i|2m6i]]</div></td></tr>
+</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2m6b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m6b OCA], [https://pdbe.org/2m6b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m6b RCSB], [https://www.ebi.ac.uk/pdbsum/2m6b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m6b ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2m6b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m6b OCA], [https://pdbe.org/2m6b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m6b RCSB], [https://www.ebi.ac.uk/pdbsum/2m6b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m6b ProSAT]</span></td></tr>
 </table>
+== Disease ==
+[https://www.uniprot.org/uniprot/GLRA1_HUMAN GLRA1_HUMAN] Defects in GLRA1 are the cause of hyperekplexia, hereditary, type 1 (HKPX1) [MIM:[https://omim.org/entry/149400 149400]. A neurologic disorder characterized by muscular rigidity of central nervous system origin, particularly in the neonatal period, and by an exaggerated startle response to unexpected acoustic or tactile stimuli.<ref>PMID:8298642</ref> [:]<ref>PMID:7925268</ref> <ref>PMID:7981700</ref> <ref>PMID:7881416</ref> <ref>PMID:7611730</ref> <ref>PMID:8571969</ref> <ref>PMID:8733061</ref> <ref>PMID:9067762</ref> <ref>PMID:10514101</ref> <ref>PMID:9920650</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/GLRA1_HUMAN GLRA1_HUMAN] The glycine receptor is a neurotransmitter-gated ion channel. Binding of glycine to its receptor increases the chloride conductance and thus produces hyperpolarization (inhibition of neuronal firing).
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 20: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Cui, T]]
+[[Category: Cui T]]
-[[Category: Jia, Y]]
+[[Category: Jia Y]]
-[[Category: Ma, D]]
+[[Category: Ma D]]
-[[Category: Makhov, A M]]
+[[Category: Makhov AM]]
-[[Category: Mowrey, D]]
+[[Category: Mowrey D]]
-[[Category: Tang, P]]
+[[Category: Tang P]]
-[[Category: Xu, Y]]
+[[Category: Xu Y]]
-[[Category: Zhang, P]]
+[[Category: Zhang P]]
-[[Category: Anion channel]]
-[[Category: Glycine receptor]]
-[[Category: Membrane protein]]
-[[Category: Transmembrane domain]]

2m6b

From Proteopedia

Revision as of 09:29, 14 June 2023

Structure of full-length transmembrane domains of human glycine receptor alpha1 monomer subunit

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox