Structures of wild-type and selected CMT1X mutant connexin 32 gap junction channels and hemichannels.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
medline:
1
9
2023
pubmed:
30
8
2023
entrez:
30
8
2023
Statut:
ppublish
Résumé
In myelinating Schwann cells, connection between myelin layers is mediated by gap junction channels (GJCs) formed by docked connexin 32 (Cx32) hemichannels (HCs). Mutations in Cx32 cause the X-linked Charcot-Marie-Tooth disease (CMT1X), a degenerative neuropathy without a cure. A molecular link between Cx32 dysfunction and CMT1X pathogenesis is still missing. Here, we describe the high-resolution cryo-electron cryo-myography (cryo-EM) structures of the Cx32 GJC and HC, along with two CMT1X-linked mutants, W3S and R22G. While the structures of wild-type and mutant GJCs are virtually identical, the HCs show a major difference: In the W3S and R22G mutant HCs, the amino-terminal gating helix partially occludes the pore, consistent with a diminished HC activity. Our results suggest that HC dysfunction may be involved in the pathogenesis of CMT1X.
Identifiants
pubmed: 37647412
doi: 10.1126/sciadv.adh4890
pmc: PMC10468125
doi:
Substances chimiques
Connexins
0
Ion Channels
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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