6fvr: Difference between revisions
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The | ==The active form of a pentameric ion channel (sTeLIC) gated by alkaline pH - sTeLIC in complex with Cesium ions (Cs+)== | ||
<StructureSection load='6fvr' size='340' side='right' caption='[[6fvr]], [[Resolution|resolution]] 4.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6fvr]] is a 5 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FVR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FVR FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BNG:B-NONYLGLUCOSIDE'>BNG</scene>, <scene name='pdbligand=CS:CESIUM+ION'>CS</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6fvr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fvr OCA], [http://pdbe.org/6fvr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fvr RCSB], [http://www.ebi.ac.uk/pdbsum/6fvr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fvr ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Pentameric ligand-gated ion channels (pLGICs) constitute a widespread class of ion channels, present in archaea, bacteria, and eukaryotes. Upon binding of their agonists in the extracellular domain, the transmembrane pore opens, allowing ions to go through, via a gating mechanism that can be modulated by a number of drugs. Even though high-resolution structural information on pLGICs has increased in a spectacular way in recent years, both in bacterial and in eukaryotic systems, the structure of the open channel conformation of some intensively studied receptors whose structures are known in a nonactive (closed) form, such as Erwinia chrysanthemi pLGIC (ELIC), is still lacking. Here we describe a gammaproteobacterial pLGIC from an endo-symbiont of Tevnia jerichonana (sTeLIC), whose sequence is closely related to the pLGIC from ELIC with 28% identity. We provide an X-ray crystallographic structure at 2.3 A in an active conformation, where the pore is found to be more open than any current conformation found for pLGICs. In addition, two charged restriction rings are present in the vestibule. Functional characterization shows sTeLIC to be a cationic channel activated at alkaline pH. It is inhibited by divalent cations, but not by quaternary ammonium ions, such as tetramethylammonium. Additionally, we found that sTeLIC is allosterically potentiated by aromatic amino acids Phe and Trp, as well as their derivatives, such as 4-bromo-cinnamate, whose cocrystal structure reveals a vestibular binding site equivalent to, but more deeply buried than, the one already described for benzodiazepines in ELIC. | |||
Crystal structures of a pentameric ion channel gated by alkaline pH show a widely open pore and identify a cavity for modulation.,Hu H, Nemecz A, Van Renterghem C, Fourati Z, Sauguet L, Corringer PJ, Delarue M Proc Natl Acad Sci U S A. 2018 Apr 24;115(17):E3959-E3968. doi:, 10.1073/pnas.1717700115. Epub 2018 Apr 9. PMID:29632192<ref>PMID:29632192</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6fvr" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Delarue, M]] | [[Category: Delarue, M]] | ||
[[Category: HU, H]] | |||
[[Category: Membrane protein]] | |||
[[Category: Pentameric ligand-gated ion channel]] | |||
Revision as of 08:38, 16 May 2018
The active form of a pentameric ion channel (sTeLIC) gated by alkaline pH - sTeLIC in complex with Cesium ions (Cs+)The active form of a pentameric ion channel (sTeLIC) gated by alkaline pH - sTeLIC in complex with Cesium ions (Cs+)
Structural highlights
Publication Abstract from PubMedPentameric ligand-gated ion channels (pLGICs) constitute a widespread class of ion channels, present in archaea, bacteria, and eukaryotes. Upon binding of their agonists in the extracellular domain, the transmembrane pore opens, allowing ions to go through, via a gating mechanism that can be modulated by a number of drugs. Even though high-resolution structural information on pLGICs has increased in a spectacular way in recent years, both in bacterial and in eukaryotic systems, the structure of the open channel conformation of some intensively studied receptors whose structures are known in a nonactive (closed) form, such as Erwinia chrysanthemi pLGIC (ELIC), is still lacking. Here we describe a gammaproteobacterial pLGIC from an endo-symbiont of Tevnia jerichonana (sTeLIC), whose sequence is closely related to the pLGIC from ELIC with 28% identity. We provide an X-ray crystallographic structure at 2.3 A in an active conformation, where the pore is found to be more open than any current conformation found for pLGICs. In addition, two charged restriction rings are present in the vestibule. Functional characterization shows sTeLIC to be a cationic channel activated at alkaline pH. It is inhibited by divalent cations, but not by quaternary ammonium ions, such as tetramethylammonium. Additionally, we found that sTeLIC is allosterically potentiated by aromatic amino acids Phe and Trp, as well as their derivatives, such as 4-bromo-cinnamate, whose cocrystal structure reveals a vestibular binding site equivalent to, but more deeply buried than, the one already described for benzodiazepines in ELIC. Crystal structures of a pentameric ion channel gated by alkaline pH show a widely open pore and identify a cavity for modulation.,Hu H, Nemecz A, Van Renterghem C, Fourati Z, Sauguet L, Corringer PJ, Delarue M Proc Natl Acad Sci U S A. 2018 Apr 24;115(17):E3959-E3968. doi:, 10.1073/pnas.1717700115. Epub 2018 Apr 9. PMID:29632192[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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