View source for 6hyr


==THE GLIC PENTAMERIC LIGAND-GATED ION CHANNEL MUTANT Q193C+MMTS==
<StructureSection load='6hyr' size='340' side='right'caption='[[6hyr]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6hyr]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Gloeobacter_violaceus_PCC_7421 Gloeobacter violaceus PCC 7421]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HYR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HYR FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</scene>, <scene name='pdbligand=SCH:S-METHYL-THIO-CYSTEINE'>SCH</scene></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=6hyr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hyr OCA], [https://pdbe.org/6hyr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hyr RCSB], [https://www.ebi.ac.uk/pdbsum/6hyr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6hyr ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GLIC_GLOVI GLIC_GLOVI] Cationic channel with similar permeabilities for Na(+) and K(+), that is activated by an increase of the proton concentration on the extracellular side. Displays no permeability for chloride ions. Shows slow kinetics of activation, no desensitization and a single channel conductance of 8 pS. Might contribute to adaptation to external pH change.<ref>PMID:17167423</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The pentameric ligand-gated ion channel (pLGIC) from Gloeobacter violaceus (GLIC) has provided insightful structure-function views on the permeation process and the allosteric regulation of the pLGICs family. However, GLIC is activated by pH instead of a neurotransmitter and a clear picture for the gating transition driven by protons is still lacking. We used an electrostatics-based (finite difference Poisson-Boltzmann/Debye-Huckel) method to predict the acidities of all aspartic and glutamic residues in GLIC, both in its active and closed-channel states. Those residues with a predicted pKa close to the experimental pH50 were individually replaced by alanine and the resulting variant receptors were titrated by ATR/FTIR spectroscopy. E35, located in front of loop F far away from the orthosteric site, appears as the key proton sensor with a measured individual pKa at 5.8. In the GLIC open conformation, E35 is connected through a water-mediated hydrogen-bond network first to the highly conserved electrostatic triad R192-D122-D32 and then to Y197-Y119-K248, both located at the extracellular domain-transmembrane domain interface. The second triad controls a cluster of hydrophobic side chains from the M2-M3 loop that is remodeled during the gating transition. We solved 12 crystal structures of GLIC mutants, 6 of them being trapped in an agonist-bound but nonconductive conformation. Combined with previous data, this reveals two branches of a continuous network originating from E35 that reach, independently, the middle transmembrane region of two adjacent subunits. We conclude that GLIC's gating proceeds by making use of loop F, already known as an allosteric site in other pLGICs, instead of the classic orthosteric site.

Electrostatics, proton sensor, and networks governing the gating transition in GLIC, a proton-gated pentameric ion channel.,Hu H, Ataka K, Menny A, Fourati Z, Sauguet L, Corringer PJ, Koehl P, Heberle J, Delarue M Proc Natl Acad Sci U S A. 2018 Dec 12. pii: 1813378116. doi:, 10.1073/pnas.1813378116. PMID:30541892<ref>PMID:30541892</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6hyr" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ion channels 3D structures|Ion channels 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Gloeobacter violaceus PCC 7421]]
[[Category: Large Structures]]
[[Category: Delarue M]]
[[Category: Hu HD]]