View source for 4ire


==Crystal structure of GLIC with mutations at the loop C region==
<StructureSection load='4ire' size='340' side='right'caption='[[4ire]], [[Resolution|resolution]] 3.19&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4ire]] 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=4IRE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IRE 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]] 3.19&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=LMD:TETRADECYL+4-O-ALPHA-D-GLUCOPYRANOSYL-BETA-D-GLUCOPYRANOSIDE'>LMD</scene>, <scene name='pdbligand=OXL:OXALATE+ION'>OXL</scene>, <scene name='pdbligand=PC1:1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE'>PC1</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=4ire FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ire OCA], [https://pdbe.org/4ire PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ire RCSB], [https://www.ebi.ac.uk/pdbsum/4ire PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ire 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 mechanisms of allosteric action within pentameric ligand-gated ion channels (pLGICs) remain to be determined. Using crystallography, site-directed mutagenesis, and two-electrode voltage clamp measurements, we identified two functionally relevant sites in the extracellular (EC) domain of the bacterial pLGIC from Gloeobacter violaceus (GLIC). One site is at the C-loop region, where the NQN mutation (D91N, E177Q, and D178N) eliminated inter-subunit salt bridges in the open-channel GLIC structure and thereby shifted the channel activation to a higher agonist concentration. The other site is below the C-loop, where binding of the anesthetic ketamine inhibited GLIC currents in a concentration dependent manner. To understand how a perturbation signal in the EC domain, either resulting from the NQN mutation or ketamine binding, is transduced to the channel gate, we have used the Perturbation-based Markovian Transmission (PMT) model to determine dynamic responses of the GLIC channel and signaling pathways upon initial perturbations in the EC domain of GLIC. Despite the existence of many possible routes for the initial perturbation signal to reach the channel gate, the PMT model in combination with Yen's algorithm revealed that perturbation signals with the highest probability flow travel either via the beta1-beta2 loop or through pre-TM1. The beta1-beta2 loop occurs in either intra- or inter-subunit pathways, while pre-TM1 occurs exclusively in inter-subunit pathways. Residues involved in both types of pathways are well supported by previous experimental data on nAChR. The direct coupling between pre-TM1 and TM2 of the adjacent subunit adds new insight into the allosteric signaling mechanism in pLGICs.

Signal transduction pathways in the pentameric ligand-gated ion channels.,Mowrey D, Chen Q, Liang Y, Liang J, Xu Y, Tang P PLoS One. 2013 May 8;8(5):e64326. doi: 10.1371/journal.pone.0064326. Print 2013. PMID:23667707<ref>PMID:23667707</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4ire" 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: Chen Q]]
[[Category: Liang YH]]
[[Category: Pan J]]
[[Category: Tang P]]
[[Category: Xu Y]]