1vry

From Proteopedia

(Difference between revisions)

Revision as of 07:39, 4 April 2018

Second and Third Transmembrane Domains of the Alpha-1 Subunit of Human Glycine Receptor

Structural highlights

1vry is a 1 chain structure with sequence from Human. This structure supersedes the now removed PDB entry 1zhd. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	GLRA1 (HUMAN)
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).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

A 61-residue polypeptide resembling the second and third transmembrane domains (TM23) of the alpha-1 subunit of human glycine receptor and its truncated form, both with the wild-type loop linking the two TM domains (the "23" loop), were studied using high-resolution NMR. Well-defined domain structures can be identified for the TM2, 23 loop, and TM3 regions. Contrary to the popular model of a long and straight alpha-helical structure for the pore-lining TM2 domain for the Cys-loop receptor family, the last three residues of the TM2 domain and the first eight residues of the 23 loop (S16-S26) seem to be intrinsically nonhelical and highly flexible even in trifluoroethanol, a solvent known to promote and stabilize alpha-helical structures. The six remaining residues of the 23 loop and most of the TM3 domain exhibit helical structures with a kinked pi-helix (or a pi-turn) from W34 to C38 and a kink angle of 159 +/- 3 degrees . The tertiary fold of TM3 relative to TM2 is defined by several unambiguously identified long-range NOE cross-peaks within the loop region and between TM2 and TM3 domains. The 20 lowest-energy structures show a left-handed tilt of TM3 relative to TM2 with a tilting angle of 44 +/- 2 degrees between TM2 (V1-Q14) and TM3 (L39-E48) helix axes. This left-handed TM2-TM3 arrangement ensures a neatly packed right-handed quaternary structure of five subunits to form an ion-conducting pore. This is the first time that two TM domains of the glycine receptor linked by the important 23 loop have ever been analyzed at atomistic resolution. Many structural characteristics of the receptor can be inferred from the structural and dynamical features identified in this study.

Structure and dynamics of the second and third transmembrane domains of human glycine receptor.,Ma D, Liu Z, Li L, Tang P, Xu Y Biochemistry. 2005 Jun 21;44(24):8790-800. PMID:15952785^[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
↑ Ma D, Liu Z, Li L, Tang P, Xu Y. Structure and dynamics of the second and third transmembrane domains of human glycine receptor. Biochemistry. 2005 Jun 21;44(24):8790-800. PMID:15952785 doi:http://dx.doi.org/10.1021/bi050256n

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1vry"

@@ Line 1: / Line 1: @@
 ==Second and Third Transmembrane Domains of the Alpha-1 Subunit of Human Glycine Receptor==
 <StructureSection load='1vry' size='340' side='right' caption='[[1vry]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[1vry]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1zhd 1zhd]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VRY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1VRY FirstGlance]. <br>
 </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GLRA1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1vry FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1vry OCA], [http://pdbe.org/1vry PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1vry RCSB], [http://www.ebi.ac.uk/pdbsum/1vry PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1vry FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1vry OCA], [http://pdbe.org/1vry PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1vry RCSB], [http://www.ebi.ac.uk/pdbsum/1vry PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1vry ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vr/1vry_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vr/1vry_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

1vry

From Proteopedia

Revision as of 07:39, 4 April 2018

Second and Third Transmembrane Domains of the Alpha-1 Subunit of Human Glycine Receptor

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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