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Title | Cryo-EM structures of human Cx36/GJD2 neuronal gap junction channel. |
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Journal, issue, pages | Nat Commun, Vol. 14, Issue 1, Page 1347, Year 2023 |
Publish date | Mar 11, 2023 |
Authors | Seu-Na Lee / Hwa-Jin Cho / Hyeongseop Jeong / Bumhan Ryu / Hyuk-Joon Lee / Minsoo Kim / Jejoong Yoo / Jae-Sung Woo / Hyung Ho Lee / |
PubMed Abstract | Connexin 36 (Cx36) is responsible for signal transmission in electrical synapses by forming interneuronal gap junctions. Despite the critical role of Cx36 in normal brain function, the molecular ...Connexin 36 (Cx36) is responsible for signal transmission in electrical synapses by forming interneuronal gap junctions. Despite the critical role of Cx36 in normal brain function, the molecular architecture of the Cx36 gap junction channel (GJC) is unknown. Here, we determine cryo-electron microscopy structures of Cx36 GJC at 2.2-3.6 Å resolutions, revealing a dynamic equilibrium between its closed and open states. In the closed state, channel pores are obstructed by lipids, while N-terminal helices (NTHs) are excluded from the pore. In the open state with pore-lining NTHs, the pore is more acidic than those in Cx26 and Cx46/50 GJCs, explaining its strong cation selectivity. The conformational change during channel opening also includes the α-to-π-helix transition of the first transmembrane helix, which weakens the protomer-protomer interaction. Our structural analyses provide high resolution information on the conformational flexibility of Cx36 GJC and suggest a potential role of lipids in the channel gating. |
External links | Nat Commun / PubMed:36906653 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.2 - 7.2 Å |
Structure data | EMDB-33254, PDB-7xki: EMDB-33255: Human Cx36/GJD2 (N-terminal deletion BRIL-fused mutant) gap junction channel in soybean lipids (C1 symmetry) EMDB-33256, PDB-7xkk: EMDB-33270, PDB-7xkt: EMDB-33274, PDB-7xl8: EMDB-33275: Human Cx36/GJD2 (N-terminal deletion mutant) gap junction channel in soybean lipids (C1 symmetry) EMDB-33315, PDB-7xnh: EMDB-33327, PDB-7xnv: EMDB-33328: Structurally hetero-junctional human Cx36/GJD2 gap junction channel in soybean lipids (C1 symmetry) EMDB-34822: Human Cx36/GJD2 (BRIL-fused mutant) gap junction channel in soybean lipids EMDB-34856, PDB-8hkp: EMDB-34857: Structurally hetero-junctional human Cx36/GJD2 gap junction channel in detergents (C1 symmetry) |
Chemicals | ChemComp-MC3: ChemComp-Y01: ChemComp-LHG: ChemComp-HOH: ChemComp-AV0: |
Source |
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Keywords | MEMBRANE PROTEIN / connexin 36 / Gap Junction Channel / Cx36 / GJD2 / BRIL |