Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
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Journal
IF	>30 >20 >10 >5 all

Title	Mefloquine-induced conformational shift in Cx36 N-terminal helix leading to channel closure mediated by lipid bilayer.
Journal, issue, pages	Nat Commun, Vol. 15, Issue 1, Page 9223, Year 2024
Publish date	Oct 25, 2024
Authors	Hwa-Jin Cho / Dong Kyu Chung / Hyung Ho Lee /
PubMed Abstract	Connexin 36 (Cx36) forms interneuronal gap junctions, establishing electrical synapses for rapid synaptic transmission. In disease conditions, inhibiting Cx36 gap junction channels (GJCs) is ...Connexin 36 (Cx36) forms interneuronal gap junctions, establishing electrical synapses for rapid synaptic transmission. In disease conditions, inhibiting Cx36 gap junction channels (GJCs) is beneficial, as it prevents abnormal synchronous neuronal firing and apoptotic signal propagation, mitigating seizures and progressive cell death. Here, we present cryo-electron microscopy structures of human Cx36 GJC in complex with known channel inhibitors, such as mefloquine, arachidonic acid, and 1-hexanol. Notably, these inhibitors competitively bind to the binding pocket of the N-terminal helices (NTH), inducing a conformational shift from the pore-lining NTH (PLN) state to the flexible NTH (FN) state. This leads to the obstruction of the channel pore by flat double-layer densities of lipids. These studies elucidate the molecular mechanisms of how Cx36 GJC can be modulated by inhibitors, providing valuable insights into potential therapeutic applications.
External links	Nat Commun / PubMed:39455592 / PubMed Central
Methods	EM (single particle)
Resolution	2.5 - 3.6 Å
Structure data	38318 8xgd EMDB-38318, PDB-8xgd: Human Cx36/GJD2 gap junction channel with pore-lining N-terminal helices in porcine brain lipids. Method: EM (single particle) / Resolution: 2.5 Å 38319 8xge EMDB-38319, PDB-8xge: Human Cx36/GJD2 gap junction channel in porcine brain lipids. Method: EM (single particle) / Resolution: 2.89 Å 38320 8xgf EMDB-38320, PDB-8xgf: Human Cx36/GJD2 gap junction channel in complex with arachidonic acid. Method: EM (single particle) / Resolution: 2.95 Å EMDB-38321: Human Cx36/GJD2 gap junction channel in complex with arachidonic acid (C1 symmetry). Method: EM (single particle) / Resolution: 3.4 Å 38322 8xgg EMDB-38322, PDB-8xgg: Human Cx36/GJD2 gap junction channel in complex with 1-hexanol. Method: EM (single particle) / Resolution: 3.2 Å EMDB-38323: Human Cx36/GJD2 gap junction channel in complex with 1-hexanol (C1 symmetry). Method: EM (single particle) / Resolution: 3.6 Å EMDB-38326: Human Cx36/GJD2 gap junction channel in complex with mefloquine. Method: EM (single particle) / Resolution: 3.2 Å 38327 8xgj EMDB-38327, PDB-8xgj: Human Cx36/GJD2 gap junction channel in complex with mefloquine. Method: EM (single particle) / Resolution: 2.7 Å 38344 8xh8 EMDB-38344, PDB-8xh8: Human Cx36/GJD2 (Ala14-deleted mutant) gap junction channel in porcine brain lipids Method: EM (single particle) / Resolution: 2.72 Å 38345 8xh9 EMDB-38345, PDB-8xh9: Human Cx36/GJD2 (Ala14 deletion mutant) gap junction channel prepared with mefloquine, showing no bound mefloquine Method: EM (single particle) / Resolution: 2.58 Å EMDB-38346: Human Cx36/GJD2 gap junction channel with pore-lining helices in porcine brain lipids (C1 symmetry) Method: EM (single particle) / Resolution: 3.1 Å EMDB-38347: Human Cx36/GJD2 gap junction channel in porcine brain lipids (C1 symmetry) Method: EM (single particle) / Resolution: 3.1 Å EMDB-38356: Human Cx36/GJD2 (Ala14-deleted mutant) gap junction channel in porcine brain lipids (C1 symmetry) Method: EM (single particle) / Resolution: 3.2 Å EMDB-38357: Human Cx36/GJD2 (Ala14 deletion mutant) gap junction channel prepared with mefloquine, showing no bound mefloquine (C1 symmetry) Method: EM (single particle) / Resolution: 3.1 Å
Chemicals	ChemComp-MC3: 1,2-DIMYRISTOYL-RAC-GLYCERO-3-PHOSPHOCHOLINE / phospholipidYM ChemComp-Y01: CHOLESTEROL HEMISUCCINATE ChemComp-ACD: ARACHIDONIC ACID ChemComp-HE2: HEXAN-1-OL ChemComp-YMZ: Mefloquine / medicationYM
Source	homo sapiens (human)
Keywords	MEMBRANE PROTEIN / connexin 36 / Cx36 / gap junction channel / GJD2 / arachidonic acid / hexanol / mefloquine