1mot

From Proteopedia

(Difference between revisions)

Revision as of 11:18, 18 December 2014

NMR Structure Of Extended Second Transmembrane Domain Of Glycine Receptor alpha1 Subunit in SDS Micelles

Structural highlights

1mot 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.
Gene:	GLRA1 (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

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

The structure and backbone dynamics of an extended second transmembrane segment (TM2e) of the human neuronal glycine receptor alpha(1) subunit in sodium dodecyl sulfate micelles were studied by (1)H and (15)N solution-state NMR. The 28-amino acid segment contained the consensus TM2 domain plus part of the linker between the second and third transmembrane domains. The presence of a well-structured helical region of at least 13 amino acids long and an unstructured region near the linker was evident from the proton chemical shifts and the pattern of midrange nuclear Overhauser effects (NOE). (15)N relaxation rate constants, R(1) and R(2), and (15)N-[(1)H] NOE indicated restricted internal motions in the helical region with NOE values between 0.6 and 0.8. The squared order parameter (S(2)), the effective correlation time for fast internal motions (tau(e)), and the global rotational correlation time (tau(m)) were calculated for all TM2e backbone N-H bonds using the model-free approach. The S(2) values ranged about 0.75-0.86, and the tau(e) values were below 100 ps for most of the residues in the helical region. The tau(m) value, calculated from the dynamics of the helical region, was 5.1 ns. The S(2) values decreased to 0.1, and the tau(e) values sharply increased up to 1.2 ns at the linker near the C-terminus, indicating that the motion of this region is unrestricted. The results suggest a relatively high degree of motional freedom of TM2e in micelles and different propensities of the N- and C-terminal moieties of the transmembrane domain to assume stable helical structures.

NMR structure and backbone dynamics of the extended second transmembrane domain of the human neuronal glycine receptor alpha1 subunit.,Yushmanov VE, Mandal PK, Liu Z, Tang P, Xu Y Biochemistry. 2003 Apr 8;42(13):3989-95. PMID:12667090^[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
↑ Yushmanov VE, Mandal PK, Liu Z, Tang P, Xu Y. NMR structure and backbone dynamics of the extended second transmembrane domain of the human neuronal glycine receptor alpha1 subunit. Biochemistry. 2003 Apr 8;42(13):3989-95. PMID:12667090 doi:10.1021/bi026767g

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/1mot"

@@ Line 1: / Line 1: @@
-{{STRUCTURE_1mot|  PDB=1mot  |  SCENE=  }}
+==NMR Structure Of Extended Second Transmembrane Domain Of Glycine Receptor alpha1 Subunit in SDS Micelles==
-===NMR Structure Of Extended Second Transmembrane Domain Of Glycine Receptor alpha1 Subunit in SDS Micelles===
+<StructureSection load='1mot' size='340' side='right' caption='[[1mot]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
-{{ABSTRACT_PUBMED_12667090}}
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1mot]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MOT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1MOT FirstGlance]. <br>
-==Disease==
+</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 Homo sapiens])</td></tr>
-[[http://www.uniprot.org/uniprot/GLRA1_HUMAN GLRA1_HUMAN]] Defects in GLRA1 are the cause of hyperekplexia, hereditary, type 1 (HKPX1) [MIM:[http://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>
+<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=1mot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mot OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1mot RCSB], [http://www.ebi.ac.uk/pdbsum/1mot PDBsum]</span></td></tr>
+</table>
-==Function==
+== Disease ==
+[[http://www.uniprot.org/uniprot/GLRA1_HUMAN GLRA1_HUMAN]] Defects in GLRA1 are the cause of hyperekplexia, hereditary, type 1 (HKPX1) [MIM:[http://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 ==
 [[http://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 ==
+The structure and backbone dynamics of an extended second transmembrane segment (TM2e) of the human neuronal glycine receptor alpha(1) subunit in sodium dodecyl sulfate micelles were studied by (1)H and (15)N solution-state NMR. The 28-amino acid segment contained the consensus TM2 domain plus part of the linker between the second and third transmembrane domains. The presence of a well-structured helical region of at least 13 amino acids long and an unstructured region near the linker was evident from the proton chemical shifts and the pattern of midrange nuclear Overhauser effects (NOE). (15)N relaxation rate constants, R(1) and R(2), and (15)N-[(1)H] NOE indicated restricted internal motions in the helical region with NOE values between 0.6 and 0.8. The squared order parameter (S(2)), the effective correlation time for fast internal motions (tau(e)), and the global rotational correlation time (tau(m)) were calculated for all TM2e backbone N-H bonds using the model-free approach. The S(2) values ranged about 0.75-0.86, and the tau(e) values were below 100 ps for most of the residues in the helical region. The tau(m) value, calculated from the dynamics of the helical region, was 5.1 ns. The S(2) values decreased to 0.1, and the tau(e) values sharply increased up to 1.2 ns at the linker near the C-terminus, indicating that the motion of this region is unrestricted. The results suggest a relatively high degree of motional freedom of TM2e in micelles and different propensities of the N- and C-terminal moieties of the transmembrane domain to assume stable helical structures.
-==About this Structure==
+NMR structure and backbone dynamics of the extended second transmembrane domain of the human neuronal glycine receptor alpha1 subunit.,Yushmanov VE, Mandal PK, Liu Z, Tang P, Xu Y Biochemistry. 2003 Apr 8;42(13):3989-95. PMID:12667090<ref>PMID:12667090</ref>
-[[1mot]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MOT OCA].
-==Reference==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-<ref group="xtra">PMID:012667090</ref><references group="xtra"/><references/>
+</div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Liu, Z.]]
+[[Category: Liu, Z]]
-[[Category: Mandal, P K.]]
+[[Category: Mandal, P K]]
-[[Category: Tang, P.]]
+[[Category: Tang, P]]
-[[Category: Xu, Y.]]
+[[Category: Xu, Y]]
-[[Category: Yushmanov, V E.]]
+[[Category: Yushmanov, V E]]
 [[Category: Glycine receptor]]
 [[Category: Membrane protein]]
 [[Category: Micelle]]
 [[Category: Second transmembrane domain]]

1mot

From Proteopedia

Revision as of 11:18, 18 December 2014

NMR Structure Of Extended Second Transmembrane Domain Of Glycine Receptor alpha1 Subunit in SDS Micelles

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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