EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Mefloquine-induced conformational shift in Cx36 N-terminal helix leading to channel closure mediated by lipid bilayer.
ジャーナル・号・ページ	Nat Commun, Vol. 15, Issue 1, Page 9223, Year 2024
掲載日	2024年10月25日
著者	Hwa-Jin Cho / Dong Kyu Chung / Hyung Ho Lee /
PubMed 要旨	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.
リンク	Nat Commun / PubMed:39455592 / PubMed Central
手法	EM (単粒子)
解像度	2.5 - 3.4 Å
構造データ	38318 8xgd EMDB-38318, PDB-8xgd: Human Cx36/GJD2 gap junction channel with pore-lining N-terminal helices in porcine brain lipids. 手法: EM (単粒子) / 解像度: 2.5 Å 38319 8xge EMDB-38319, PDB-8xge: Human Cx36/GJD2 gap junction channel in porcine brain lipids. 手法: EM (単粒子) / 解像度: 2.89 Å 38320 8xgf EMDB-38320, PDB-8xgf: Human Cx36/GJD2 gap junction channel in complex with arachidonic acid. 手法: EM (単粒子) / 解像度: 2.95 Å EMDB-38321: Human Cx36/GJD2 gap junction channel in complex with arachidonic acid (C1 symmetry). 手法: EM (単粒子) / 解像度: 3.4 Å 38322 8xgg EMDB-38322, PDB-8xgg: Human Cx36/GJD2 gap junction channel in complex with 1-hexanol. 手法: EM (単粒子) / 解像度: 3.2 Å EMDB-38326: Human Cx36/GJD2 gap junction channel in complex with mefloquine. 手法: EM (単粒子) / 解像度: 3.2 Å 38327 8xgj EMDB-38327, PDB-8xgj: Human Cx36/GJD2 gap junction channel in complex with mefloquine. 手法: EM (単粒子) / 解像度: 2.7 Å 38344 8xh8 EMDB-38344, PDB-8xh8: Human Cx36/GJD2 (Ala14-deleted mutant) gap junction channel in porcine brain lipids 手法: EM (単粒子) / 解像度: 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 手法: EM (単粒子) / 解像度: 2.58 Å EMDB-38346: Human Cx36/GJD2 gap junction channel with pore-lining helices in porcine brain lipids (C1 symmetry) 手法: EM (単粒子) / 解像度: 3.1 Å EMDB-38347: Human Cx36/GJD2 gap junction channel in porcine brain lipids (C1 symmetry) 手法: EM (単粒子) / 解像度: 3.1 Å EMDB-38356: Human Cx36/GJD2 (Ala14-deleted mutant) gap junction channel in porcine brain lipids (C1 symmetry) 手法: EM (単粒子) / 解像度: 3.2 Å EMDB-38357: Human Cx36/GJD2 (Ala14 deletion mutant) gap junction channel prepared with mefloquine, showing no bound mefloquine (C1 symmetry) 手法: EM (単粒子) / 解像度: 3.1 Å
化合物	ChemComp-MC3: 1,2-DIMYRISTOYL-RAC-GLYCERO-3-PHOSPHOCHOLINE / リン脂質YM ChemComp-Y01: CHOLESTEROL HEMISUCCINATE / コレステリルヘミスクシナ-ト ChemComp-ACD: ARACHIDONIC ACID / アラキドン酸 ChemComp-HE2: HEXAN-1-OL / ヘキサノ-ル ChemComp-YMZ: Mefloquine / (+)-メフロキン / 薬剤YM
由来	homo sapiens (ヒト)
キーワード	MEMBRANE PROTEIN / connexin 36 / Cx36 / gap junction channel / GJD2 / arachidonic acid / hexanol / mefloquine