9qnf

From Proteopedia

Connexin-32 (Cx32) in MSP2N2 nanodiscs with POPC

Structural highlights

9qnf is a 12 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.16Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

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

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.GFP_AEQVI Energy-transfer acceptor. Its role is to transduce the blue chemiluminescence of the protein aequorin into green fluorescent light by energy transfer. Fluoresces in vivo upon receiving energy from the Ca(2+)-activated photoprotein aequorin.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

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