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基本情報
登録情報 | データベース: PDB / ID: 7xqb | ||||||
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タイトル | Structure of connexin43/Cx43/GJA1 gap junction intercellular channel in POPE/CHS nanodiscs at pH ~8.0 | ||||||
![]() | Gap junction alpha-1 protein | ||||||
![]() | MEMBRANE PROTEIN / Cx43 / Connexin / Gap junction channel / Gating mechanism | ||||||
機能・相同性 | ![]() gap junction channel activity involved in cardiac conduction electrical coupling / negative regulation of gonadotropin secretion / positive regulation of morphogenesis of an epithelium / positive regulation of mesodermal cell differentiation / cell communication by electrical coupling / negative regulation of trophoblast cell migration / microtubule-based transport / gap junction hemi-channel activity / SARS-CoV-2 targets PDZ proteins in cell-cell junction / gap junction channel activity involved in cell communication by electrical coupling ...gap junction channel activity involved in cardiac conduction electrical coupling / negative regulation of gonadotropin secretion / positive regulation of morphogenesis of an epithelium / positive regulation of mesodermal cell differentiation / cell communication by electrical coupling / negative regulation of trophoblast cell migration / microtubule-based transport / gap junction hemi-channel activity / SARS-CoV-2 targets PDZ proteins in cell-cell junction / gap junction channel activity involved in cell communication by electrical coupling / monoatomic ion transmembrane transporter activity / Oligomerization of connexins into connexons / Transport of connexins along the secretory pathway / glutathione transmembrane transporter activity / Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane / gap junction assembly / atrial cardiac muscle cell action potential / Regulation of gap junction activity / cardiac conduction system development / connexin complex / gap junction / Formation of annular gap junctions / cell-cell contact zone / Golgi-associated vesicle membrane / cell communication by electrical coupling involved in cardiac conduction / Gap junction degradation / bone remodeling / Gap junction assembly / gap junction channel activity / export across plasma membrane / glutamate secretion / tight junction / xenobiotic transport / Mechanical load activates signaling by PIEZO1 and integrins in osteocytes / maintenance of blood-brain barrier / positive regulation of stem cell proliferation / RHOJ GTPase cycle / RHOQ GTPase cycle / establishment of mitotic spindle orientation / efflux transmembrane transporter activity / intercalated disc / alpha-tubulin binding / positive regulation of vascular associated smooth muscle cell proliferation / tubulin binding / negative regulation of cell growth / bone development / beta-catenin binding / cellular response to amyloid-beta / cell junction / intracellular protein localization / cell-cell signaling / positive regulation of cold-induced thermogenesis / heart development / monoatomic ion transmembrane transport / spermatogenesis / positive regulation of canonical NF-kappaB signal transduction / apical plasma membrane / membrane raft / Golgi membrane / focal adhesion / intracellular membrane-bounded organelle / endoplasmic reticulum membrane / positive regulation of gene expression / Golgi apparatus / signal transduction / mitochondrion / nucleoplasm / nucleus / plasma membrane / cytoplasm 類似検索 - 分子機能 | ||||||
生物種 | ![]() | ||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3 Å | ||||||
![]() | Lee, H.J. / Cha, H.J. / Jeong, H. / Lee, S.N. / Lee, C.W. / Woo, J.S. | ||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Conformational changes in the human Cx43/GJA1 gap junction channel visualized using cryo-EM. 著者: Hyuk-Joon Lee / Hyung Jin Cha / Hyeongseop Jeong / Seu-Na Lee / Chang-Won Lee / Minsoo Kim / Jejoong Yoo / Jae-Sung Woo / ![]() 要旨: Connexin family proteins assemble into hexameric hemichannels in the cell membrane. The hemichannels dock together between two adjacent membranes to form gap junction intercellular channels (GJIChs). ...Connexin family proteins assemble into hexameric hemichannels in the cell membrane. The hemichannels dock together between two adjacent membranes to form gap junction intercellular channels (GJIChs). We report the cryo-electron microscopy structures of Cx43 GJICh, revealing the dynamic equilibrium state of various channel conformations in detergents and lipid nanodiscs. We identify three different N-terminal helix conformations of Cx43-gate-covering (GCN), pore-lining (PLN), and flexible intermediate (FIN)-that are randomly distributed in purified GJICh particles. The conformational equilibrium shifts to GCN by cholesteryl hemisuccinates and to PLN by C-terminal truncations and at varying pH. While GJIChs that mainly comprise GCN protomers are occluded by lipids, those containing conformationally heterogeneous protomers show markedly different pore sizes. We observe an α-to-π-helix transition in the first transmembrane helix, which creates a side opening to the membrane in the FIN and PLN conformations. This study provides basic structural information to understand the mechanisms of action and regulation of Cx43 GJICh. | ||||||
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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PDBx/mmCIF形式 | ![]() | 1.2 MB | 表示 | ![]() |
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PDB形式 | ![]() | 994 KB | 表示 | ![]() |
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-検証レポート
文書・要旨 | ![]() | 2.9 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 2.9 MB | 表示 | |
XML形式データ | ![]() | 109 KB | 表示 | |
CIF形式データ | ![]() | 123.5 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 33392MC ![]() 7f92C ![]() 7f93C ![]() 7f94C ![]() 7xq9C ![]() 7xqdC ![]() 7xqfC ![]() 7xqgC ![]() 7xqhC ![]() 7xqiC ![]() 7xqjC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
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集合体
登録構造単位 | ![]()
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要素
#1: タンパク質 | 分子量: 43061.336 Da / 分子数: 12 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #2: 化合物 | ChemComp-C14 / #3: 化合物 | ChemComp-Y01 / #4: 化合物 | ChemComp-PTY / 研究の焦点であるリガンドがあるか | Y | Has protein modification | Y | |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
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試料調製
構成要素 | 名称: Dodecameric complex of human Cx43/GJA1 in lipid nanodiscs (POPE/CHS) タイプ: COMPLEX 詳細: Human Cx43 gap junction channel with gate-covering NTH conformation Entity ID: #1 / 由来: RECOMBINANT |
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由来(天然) | 生物種: ![]() |
由来(組換発現) | 生物種: ![]() |
緩衝液 | pH: 8 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
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電子顕微鏡撮影
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2750 nm / 最小 デフォーカス(公称値): 1250 nm |
撮影 | 電子線照射量: 40 e/Å2 フィルム・検出器のモデル: FEI FALCON III (4k x 4k) |
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解析
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 21621 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
精密化 | 交差検証法: NONE | ||||||||||||||||||||||||
拘束条件 |
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