4lmj: Difference between revisions
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== | ==GLIC Liganded-closed-channel Conformation, Mutant T25'A== | ||
[[http://www.uniprot.org/uniprot/GLIC_GLOVI GLIC_GLOVI | <StructureSection load='4lmj' size='340' side='right'caption='[[4lmj]], [[Resolution|resolution]] 3.44Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4lmj]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Gloeobacter_violaceus Gloeobacter violaceus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LMJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LMJ 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]] 3.44Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=4lmj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lmj OCA], [https://pdbe.org/4lmj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lmj RCSB], [https://www.ebi.ac.uk/pdbsum/4lmj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lmj 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 == | |||
Cryoelectron microscopy and X-ray crystallography have recently been used to generate structural models that likely represent the unliganded closed-channel conformation and the fully liganded open-channel conformation of different members of the nicotinic-receptor superfamily. To characterize the structure of the closed-channel conformation in its liganded state, we identified a number of positions in the loop between transmembrane segments 2 (M2) and 3 (M3) of a proton-gated ortholog from the bacterium Gloeobacter violaceus (GLIC) where mutations to alanine reduce the liganded-gating equilibrium constant, and solved the crystal structures of two such mutants (T25'A and Y27'A) at pH approximately 4.0. At the level of backbone atoms, the liganded closed-channel model presented here differs from the liganded open-channel structure of GLIC in the pre-M1 linker, the M3-M4 loop, and much more prominently, in the extracellular half of the pore lining, where the more pronounced tilt of the closed-channel M2 alpha-helices toward the pore's long axis narrows the permeation pathway. On the other hand, no differences between the liganded closed-channel and open-channel models could be detected at the level of the extracellular domain, where conformational changes are expected to underlie the low-to-high proton-affinity switch that drives gating of proton-bound channels. Thus, the liganded closed-channel model is nearly indistinguishable from the recently described "locally closed" structure. However, because cross-linking strategies (which could have stabilized unstable conformations) and mutations involving ionizable side chains (which could have affected proton-gated channel activation) were purposely avoided, we favor the notion that this structure represents one of the end states of liganded gating rather than an unstable intermediate. | |||
Gating of the proton-gated ion channel from Gloeobacter violaceus at pH 4 as revealed by X-ray crystallography.,Gonzalez-Gutierrez G, Cuello LG, Nair SK, Grosman C Proc Natl Acad Sci U S A. 2013 Oct 28. PMID:24167270<ref>PMID:24167270</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
< | </div> | ||
[[ | <div class="pdbe-citations 4lmj" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
[[Category: | *[[Ion channels 3D structures|Ion channels 3D structures]] | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
</StructureSection> | |||
[[Category: Gloeobacter violaceus]] | |||
[[Category: Large Structures]] | |||
[[Category: Gonzalez-Gutierrez G]] | |||
[[Category: Grosman C]] | |||
Latest revision as of 19:21, 20 September 2023
GLIC Liganded-closed-channel Conformation, Mutant T25'AGLIC Liganded-closed-channel Conformation, Mutant T25'A
Structural highlights
FunctionGLIC_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.[1] Publication Abstract from PubMedCryoelectron microscopy and X-ray crystallography have recently been used to generate structural models that likely represent the unliganded closed-channel conformation and the fully liganded open-channel conformation of different members of the nicotinic-receptor superfamily. To characterize the structure of the closed-channel conformation in its liganded state, we identified a number of positions in the loop between transmembrane segments 2 (M2) and 3 (M3) of a proton-gated ortholog from the bacterium Gloeobacter violaceus (GLIC) where mutations to alanine reduce the liganded-gating equilibrium constant, and solved the crystal structures of two such mutants (T25'A and Y27'A) at pH approximately 4.0. At the level of backbone atoms, the liganded closed-channel model presented here differs from the liganded open-channel structure of GLIC in the pre-M1 linker, the M3-M4 loop, and much more prominently, in the extracellular half of the pore lining, where the more pronounced tilt of the closed-channel M2 alpha-helices toward the pore's long axis narrows the permeation pathway. On the other hand, no differences between the liganded closed-channel and open-channel models could be detected at the level of the extracellular domain, where conformational changes are expected to underlie the low-to-high proton-affinity switch that drives gating of proton-bound channels. Thus, the liganded closed-channel model is nearly indistinguishable from the recently described "locally closed" structure. However, because cross-linking strategies (which could have stabilized unstable conformations) and mutations involving ionizable side chains (which could have affected proton-gated channel activation) were purposely avoided, we favor the notion that this structure represents one of the end states of liganded gating rather than an unstable intermediate. Gating of the proton-gated ion channel from Gloeobacter violaceus at pH 4 as revealed by X-ray crystallography.,Gonzalez-Gutierrez G, Cuello LG, Nair SK, Grosman C Proc Natl Acad Sci U S A. 2013 Oct 28. PMID:24167270[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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