9z8f: Difference between revisions
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==Destabilized open state sheep connexin-46 in DMPC nanodiscs at neutral pH== | |||
<StructureSection load='9z8f' size='340' side='right'caption='[[9z8f]], [[Resolution|resolution]] 2.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9z8f]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Ovis_aries Ovis aries]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9Z8F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9Z8F FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MC3:1,2-DIMYRISTOYL-RAC-GLYCERO-3-PHOSPHOCHOLINE'>MC3</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=9z8f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9z8f OCA], [https://pdbe.org/9z8f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9z8f RCSB], [https://www.ebi.ac.uk/pdbsum/9z8f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9z8f ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CXA3_SHEEP CXA3_SHEEP] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Gap junctions, formed by connexin proteins, establish direct electrical and metabolic coupling between cells, enabling coordinated tissue responses. These channels universally respond to intracellular pH changes, closing under acidic conditions to limit the spread of cytotoxic signals during cellular stress, such as ischemia. Using cryo-electron microscopy (cryo-EM), we uncover insights into the structural mechanism of pH-gating in native lens connexin-46/50 (Cx46/50) gap junctions. Mild acidification drives lipid infiltration into the channel pore, displacing the N-terminal (NT) domain and stabilizing pore closure. Lipid involvement is shown to be both essential and fully reversible. Structural transitions involve an ensemble of gated states formed through non-cooperative NT domain movement as well as minor populations of a distinct destabilized open-state. These findings provide molecular insights into pH-gating dynamics, illustrating how structural changes may regulate gap junction function under cellular stress and linking Cx46/50 dysregulation to age-related cataract formation. | |||
Reversible lipid-mediated pH-gating of connexin-46/50 by cryo-EM.,Jarodsky JM, Myers JB, Reichow SL Nat Commun. 2026 Jan 12. doi: 10.1038/s41467-026-68311-9. PMID:41526355<ref>PMID:41526355</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Jarodsky | <div class="pdbe-citations 9z8f" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Ovis aries]] | |||
[[Category: Jarodsky JM]] | |||
[[Category: Myers JB]] | |||
[[Category: Reichow SL]] | |||
Latest revision as of 14:52, 10 February 2026
Destabilized open state sheep connexin-46 in DMPC nanodiscs at neutral pH
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