View source for 9qnd


==Connexin-32 (Cx32) W3S mutant gap junction channel in POPC-containing MSP2N2 nanodiscs==
<StructureSection load='9qnd' size='340' side='right'caption='[[9qnd]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9qnd]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Aequorea_victoria Aequorea victoria] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9QND OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9QND 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]] 2.35&#8491;</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=9qnd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9qnd OCA], [https://pdbe.org/9qnd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9qnd RCSB], [https://www.ebi.ac.uk/pdbsum/9qnd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9qnd ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/CXB1_HUMAN CXB1_HUMAN] X-linked Charcot-Marie-Tooth disease type 1;X-linked progressive cerebellar ataxia. The disease is caused by mutations affecting the gene represented in this entry.  The gene represented in this entry may act as a disease modifier.
== Function ==
[https://www.uniprot.org/uniprot/CXB1_HUMAN CXB1_HUMAN] One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Connexin-32 (Cx32) gap junction channels (GJCs) mediate intercellular coupling in various tissues, including myelinating Schwann cells. Mutations in Cx32, such as W3S, are associated with X-linked Charcot-Marie-Tooth (CMT1X) disease. Lipids regulate Cx32 GJC permeation, although the regulatory mechanism is unclear. Here, we determine the cryo-EM structures of Cx32 GJCs reconstituted in nanodiscs, revealing that phospholipids block the Cx32 GJC pore by binding to the site formed by N-terminal gating helices. The phospholipid-bound state is contingent on the presence of a sterol molecule in a hydrophobic pocket formed by the N-terminus: the N-terminal helix of Cx32 fails to sustain a phospholipid binding site in the absence of cholesterol hemisuccinate. The CMT1X-linked W3S mutant which has an impaired sterol binding site adopts a conformation of the N-terminus incompatible with phospholipid binding. Our results indicate that different lipid species control connexin channel gating directly by influencing the conformation of the N-terminal gating helix.

Lipid dependence of connexin-32 gap junction channel conformations.,Lavriha P, Fluri C, Hernandez Gonzalez JE, Korkhov VM Nat Commun. 2025 Dec 5. doi: 10.1038/s41467-025-67004-z. PMID:41350533<ref>PMID:41350533</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9qnd" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Aequorea victoria]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Fluri C]]
[[Category: Korkhov VM]]
[[Category: Lavriha P]]