View source for 2m6b


==Structure of full-length transmembrane domains of human glycine receptor alpha1 monomer subunit==
<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/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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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).
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== 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<ref>PMID:23994010</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2m6b" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cui T]]
[[Category: Jia Y]]
[[Category: Ma D]]
[[Category: Makhov AM]]
[[Category: Mowrey D]]
[[Category: Tang P]]
[[Category: Xu Y]]
[[Category: Zhang P]]