+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6u9v | |||||||||
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タイトル | Cryo electron microscopy structure of the ATP-gated rat P2X7 ion channel in the apo, closed state | |||||||||
要素 | P2X purinoceptor 7 | |||||||||
キーワード | MEMBRANE PROTEIN / Ion Channel Apoptosis | |||||||||
機能・相同性 | 機能・相同性情報 The NLRP3 inflammasome / regulation of presynaptic dense core granule exocytosis / Platelet homeostasis / positive regulation of lymphocyte apoptotic process / positive regulation of bleb assembly / NAD transport / phagolysosome assembly / Elevation of cytosolic Ca2+ levels / phospholipid transfer to membrane / positive regulation of cytoskeleton organization ...The NLRP3 inflammasome / regulation of presynaptic dense core granule exocytosis / Platelet homeostasis / positive regulation of lymphocyte apoptotic process / positive regulation of bleb assembly / NAD transport / phagolysosome assembly / Elevation of cytosolic Ca2+ levels / phospholipid transfer to membrane / positive regulation of cytoskeleton organization / purinergic nucleotide receptor activity / extracellularly ATP-gated monoatomic cation channel activity / lymphocyte apoptotic process / purinergic nucleotide receptor signaling pathway / gamma-aminobutyric acid secretion / positive regulation of monoatomic ion transmembrane transport / pore complex assembly / positive regulation of interleukin-1 alpha production / negative regulation of cell volume / plasma membrane organization / positive regulation of gamma-aminobutyric acid secretion / ATP export / : / collagen metabolic process / bleb / plasma membrane phospholipid scrambling / response to fluid shear stress / positive regulation of prostaglandin secretion / T cell apoptotic process / bleb assembly / ceramide biosynthetic process / mitochondrial depolarization / vesicle budding from membrane / programmed cell death / positive regulation of T cell apoptotic process / prostaglandin secretion / positive regulation of ossification / cellular response to dsRNA / glutamate secretion / cell volume homeostasis / positive regulation of glutamate secretion / negative regulation of bone resorption / positive regulation of macrophage cytokine production / skeletal system morphogenesis / phospholipid translocation / channel activity / negative regulation of MAPK cascade / response to ATP / positive regulation of calcium ion transport into cytosol / positive regulation of mitochondrial depolarization / response to zinc ion / T cell homeostasis / synaptic vesicle exocytosis / monoatomic cation transport / membrane depolarization / : / membrane protein ectodomain proteolysis / cellular response to organic cyclic compound / neuronal action potential / protein secretion / positive regulation of bone mineralization / T cell proliferation / response to electrical stimulus / response to mechanical stimulus / regulation of sodium ion transport / extrinsic apoptotic signaling pathway / release of sequestered calcium ion into cytosol / homeostasis of number of cells within a tissue / sensory perception of pain / positive regulation of glycolytic process / reactive oxygen species metabolic process / protein serine/threonine kinase activator activity / mitochondrion organization / positive regulation of interleukin-1 beta production / establishment of localization in cell / positive regulation of protein secretion / lipopolysaccharide binding / apoptotic signaling pathway / calcium ion transmembrane transport / response to bacterium / response to calcium ion / protein catabolic process / neuromuscular junction / cell morphogenesis / terminal bouton / response to organic cyclic compound / T cell mediated cytotoxicity / protein processing / positive regulation of T cell mediated cytotoxicity / positive regulation of interleukin-6 production / nuclear envelope / calcium ion transport / MAPK cascade / cell-cell junction / signaling receptor activity / gene expression / scaffold protein binding / postsynapse / response to lipopolysaccharide / positive regulation of MAPK cascade 類似検索 - 分子機能 | |||||||||
生物種 | Rattus norvegicus (ドブネズミ) | |||||||||
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: 2.9 Å | |||||||||
データ登録者 | Mansoor, S.E. / McCarthy, A.E. | |||||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: Cell / 年: 2019 タイトル: Full-Length P2X Structures Reveal How Palmitoylation Prevents Channel Desensitization. 著者: Alanna E McCarthy / Craig Yoshioka / Steven E Mansoor / 要旨: P2X receptors are trimeric, non-selective cation channels activated by extracellular ATP. The P2X receptor subtype is a pharmacological target because of involvement in apoptotic, inflammatory, and ...P2X receptors are trimeric, non-selective cation channels activated by extracellular ATP. The P2X receptor subtype is a pharmacological target because of involvement in apoptotic, inflammatory, and tumor progression pathways. It is the most structurally and functionally distinct P2X subtype, containing a unique cytoplasmic domain critical for the receptor to initiate apoptosis and not undergo desensitization. However, lack of structural information about the cytoplasmic domain has hindered understanding of the molecular mechanisms underlying these processes. We report cryoelectron microscopy structures of full-length rat P2X receptor in apo and ATP-bound states. These structures reveal how one cytoplasmic element, the C-cys anchor, prevents desensitization by anchoring the pore-lining helix to the membrane with palmitoyl groups. They show a second cytoplasmic element with a unique fold, the cytoplasmic ballast, which unexpectedly contains a zinc ion complex and a guanosine nucleotide binding site. Our structures provide first insights into the architecture and function of a P2X receptor cytoplasmic domain. | |||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 6u9v.cif.gz | 571.3 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6u9v.ent.gz | 489.2 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6u9v.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/u9/6u9v ftp://data.pdbj.org/pub/pdb/validation_reports/u9/6u9v | HTTPS FTP |
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-関連構造データ
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
-タンパク質 , 1種, 3分子 ABC
#1: タンパク質 | 分子量: 69904.016 Da / 分子数: 3 / 由来タイプ: 組換発現 / 由来: (組換発現) Rattus norvegicus (ドブネズミ) / 遺伝子: P2rx7 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q64663 |
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-糖 , 3種, 18分子
#2: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #3: 多糖 | #6: 糖 | ChemComp-NAG / |
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-非ポリマー , 4種, 30分子
#4: 化合物 | #5: 化合物 | ChemComp-ZN / #7: 化合物 | #8: 化合物 | ChemComp-PLM / |
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-詳細
研究の焦点であるリガンドがあるか | 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 |
-試料調製
構成要素 | 名称: P2X7 receptor ion channel / タイプ: COMPLEX / Entity ID: #1 / 由来: RECOMBINANT |
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分子量 | 実験値: NO |
由来(天然) | 生物種: Rattus norvegicus (ドブネズミ) |
由来(組換発現) | 生物種: Homo sapiens (ヒト) |
緩衝液 | pH: 7 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
試料支持 | 詳細: unspecified |
急速凍結 | 凍結剤: ETHANE |
-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: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 電子線照射量: 27 e/Å2 フィルム・検出器のモデル: FEI FALCON III (4k x 4k) |
-解析
CTF補正 | タイプ: PHASE FLIPPING ONLY |
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3次元再構成 | 解像度: 2.9 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 77697 / 対称性のタイプ: POINT |