7ZXT

cryo-EM structure of Connexin 32 W3S mutation hemi channel

Summary for 7ZXT

• Entry DOI: 10.2210/pdb7zxt/pdb
• EMDB information: 15016
• Descriptor: Gap junction beta-1 protein (1 entity in total)
• Functional Keywords: connexin, gap junction channel, cell communication, membrane protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 6
• Total formula weight: 191798.40

Authors

Qi, C.,Korkhov, V.M. (deposition date: 2022-05-22, release date: 2023-05-31, Last modification date: 2024-11-13)

Primary citation

Qi, C.,Lavriha, P.,Bayraktar, E.,Vaithia, A.,Schuster, D.,Pannella, M.,Sala, V.,Picotti, P.,Bortolozzi, M.,Korkhov, V.M.
Structures of wild-type and selected CMT1X mutant connexin 32 gap junction channels and hemichannels.
Sci Adv, 9:eadh4890-eadh4890, 2023

PubMed Abstract: 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.

PubMed: 37647412
DOI: 10.1126/sciadv.adh4890

Experimental method

ELECTRON MICROSCOPY (2.9 Å)