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| ==An open conformation of a Pentameic ligand-gated ion channel with additional N-terminal domain== | | ==An open conformation of a Pentameic ligand-gated ion channel with additional N-terminal domain== |
| <StructureSection load='6v4a' size='340' side='right'caption='[[6v4a]], [[Resolution|resolution]] 3.83Å' scene=''> | | <StructureSection load='6v4a' size='340' side='right'caption='[[6v4a]]' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[6v4a]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Uncultured_desulfofustis_sp._pb-srb1 Uncultured desulfofustis sp. pb-srb1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V4A OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6V4A FirstGlance]. <br> | | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V4A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6V4A FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P3A:PHOSPHATIDYLGLYCEROL-PHOSPHOGLYCEROL'>P3A</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction</td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">N839_03575 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1385624 uncultured Desulfofustis sp. PB-SRB1])</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=6v4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v4a OCA], [https://pdbe.org/6v4a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6v4a RCSB], [https://www.ebi.ac.uk/pdbsum/6v4a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6v4a ProSAT]</span></td></tr> |
| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6v4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v4a OCA], [http://pdbe.org/6v4a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6v4a RCSB], [http://www.ebi.ac.uk/pdbsum/6v4a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6v4a ProSAT]</span></td></tr> | |
| </table> | | </table> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Pentameric ligand-gated ion channels (pLGICs) are allosteric receptors that mediate rapid electrochemical signal transduction in the animal nervous system through the opening of an ion pore upon binding of neurotransmitters. Orthologs have been found and characterized in prokaryotes and they display highly similar structure-function relationships to eukaryotic pLGICs; however, they often encode greater architectural diversity involving additional amino-terminal domains (NTDs). Here we report structural, functional, and normal-mode analysis of two conformational states of a multidomain pLGIC, called DeCLIC, from a Desulfofustis deltaproteobacterium, including a periplasmic NTD fused to the conventional ligand-binding domain (LBD). X-ray structure determination revealed an NTD consisting of two jelly-roll domains interacting across each subunit interface. Binding of Ca(2+) at the LBD subunit interface was associated with a closed transmembrane pore, with resolved monovalent cations intracellular to the hydrophobic gate. Accordingly, DeCLIC-injected oocytes conducted currents only upon depletion of extracellular Ca(2+); these were insensitive to quaternary ammonium block. Furthermore, DeCLIC crystallized in the absence of Ca(2+) with a wide-open pore and remodeled periplasmic domains, including increased contacts between the NTD and classic LBD agonist-binding sites. Functional, structural, and dynamical properties of DeCLIC paralleled those of sTeLIC, a pLGIC from another symbiotic prokaryote. Based on these DeCLIC structures, we would reclassify the previous structure of bacterial ELIC (the first high-resolution structure of a pLGIC) as a "locally closed" conformation. Taken together, structures of DeCLIC in multiple conformations illustrate dramatic conformational state transitions and diverse regulatory mechanisms available to ion channels in pLGICs, particularly involving Ca(2+) modulation and periplasmic NTDs.
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| Structural basis for allosteric transitions of a multidomain pentameric ligand-gated ion channel.,Hu H, Howard RJ, Bastolla U, Lindahl E, Delarue M Proc Natl Acad Sci U S A. 2020 Jun 1. pii: 1922701117. doi:, 10.1073/pnas.1922701117. PMID:32482881<ref>PMID:32482881</ref>
| | ==See Also== |
| | | *[[Ion channels 3D structures|Ion channels 3D structures]] |
| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 6v4a" style="background-color:#fffaf0;"></div>
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| == References == | |
| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Uncultured desulfofustis sp. pb-srb1]]
| | [[Category: Delarue, M, Hu, HD]] |
| [[Category: Delarue, M]] | |
| [[Category: Hu, H D]]
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| [[Category: Pentameric ligand-gated ion channel]]
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| [[Category: Transport protein]]
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