+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8dn5 | ||||||
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タイトル | Cryo-EM structure of human Glycine Receptor alpha1-beta heteromer, glycine-bound state1(open state) | ||||||
要素 | (Glycine receptor subunit ...) x 2 | ||||||
キーワード | MEMBRANE PROTEIN / glycine receptor subunit alpha-1 / glycine receptor subunit beta / Green fluorescent protein | ||||||
機能・相同性 | 機能・相同性情報 taurine binding / negative regulation of transmission of nerve impulse / acrosome reaction / positive regulation of acrosome reaction / glycine-gated chloride channel complex / synaptic transmission, glycinergic / gamma-aminobutyric acid receptor clustering / Neurotransmitter receptors and postsynaptic signal transmission / postsynaptic specialization / neuromuscular process controlling posture ...taurine binding / negative regulation of transmission of nerve impulse / acrosome reaction / positive regulation of acrosome reaction / glycine-gated chloride channel complex / synaptic transmission, glycinergic / gamma-aminobutyric acid receptor clustering / Neurotransmitter receptors and postsynaptic signal transmission / postsynaptic specialization / neuromuscular process controlling posture / extracellularly glycine-gated ion channel activity / inhibitory synapse / regulation of respiratory gaseous exchange by nervous system process / righting reflex / response to alcohol / extracellularly glycine-gated chloride channel activity / glycinergic synapse / inhibitory postsynaptic potential / cellular response to ethanol / chloride transport / adult walking behavior / cellular response to zinc ion / neurotransmitter receptor activity / glycine binding / startle response / chloride channel complex / neuropeptide signaling pathway / neuronal action potential / transmembrane transporter complex / GABA-ergic synapse / monoatomic ion transport / muscle contraction / chloride transmembrane transport / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / visual perception / bioluminescence / regulation of membrane potential / generation of precursor metabolites and energy / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / cellular response to amino acid stimulus / transmembrane signaling receptor activity / nervous system development / chemical synaptic transmission / perikaryon / postsynaptic membrane / neuron projection / external side of plasma membrane / intracellular membrane-bounded organelle / neuronal cell body / dendrite / synapse / protein-containing complex binding / zinc ion binding / identical protein binding / membrane / plasma membrane / cytoplasm 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) Aequorea victoria (オワンクラゲ) | ||||||
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: 3.63 Å | ||||||
データ登録者 | Liu, X. / Wang, W. | ||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: Nat Commun / 年: 2023 タイトル: Asymmetric gating of a human hetero-pentameric glycine receptor. 著者: Xiaofen Liu / Weiwei Wang / 要旨: Hetero-pentameric Cys-loop receptors constitute a major type of neurotransmitter receptors that enable signal transmission and processing in the nervous system. Despite intense investigations into ...Hetero-pentameric Cys-loop receptors constitute a major type of neurotransmitter receptors that enable signal transmission and processing in the nervous system. Despite intense investigations into their working mechanism and pharmaceutical potentials, how neurotransmitters activate these receptors remains unclear due to the lack of high-resolution structural information in the activated open state. Here we report near-atomic resolution structures resolved in digitonin consistent with all principle functional states of the human α1β GlyR, which is a major Cys-loop receptor that mediates inhibitory neurotransmission in the central nervous system of adults. Glycine binding induces cooperative and symmetric structural rearrangements in the neurotransmitter-binding extracellular domain but asymmetrical pore dilation in the transmembrane domain. Symmetric response in the extracellular domain is consistent with electrophysiological data showing cooperative glycine activation and contribution from both α1 and β subunits. A set of functionally essential but differentially charged amino acid residues in the transmembrane domain of the α1 and β subunits explains asymmetric activation. These findings provide a foundation for understanding how the gating of the Cys-loop receptor family members diverges to accommodate specific physiological environments. | ||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 8dn5.cif.gz | 342.1 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8dn5.ent.gz | 276.2 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8dn5.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
文書・要旨 | 8dn5_validation.pdf.gz | 1.6 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 8dn5_full_validation.pdf.gz | 1.6 MB | 表示 | |
XML形式データ | 8dn5_validation.xml.gz | 62.1 KB | 表示 | |
CIF形式データ | 8dn5_validation.cif.gz | 87.5 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/dn/8dn5 ftp://data.pdbj.org/pub/pdb/validation_reports/dn/8dn5 | HTTPS FTP |
-関連構造データ
-リンク
-集合体
登録構造単位 |
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-要素
-Glycine receptor subunit ... , 2種, 5分子 DABCE
#1: タンパク質 | 分子量: 42421.113 Da / 分子数: 4 / 由来タイプ: 組換発現 詳細: Derived by substitution of M3/M4 loop (residues R316-P381) s by GSSG peptide. 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GLRA1 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P23415 #2: タンパク質 | | 分子量: 76584.531 Da / 分子数: 1 / 由来タイプ: 組換発現 由来: (組換発現) Homo sapiens (ヒト), (組換発現) Aequorea victoria (オワンクラゲ) 遺伝子: GLRB, GFP / 発現宿主: Homo sapiens (ヒト) 参照: UniProt: P48167, UniProt: P42212, UniProt: A0A2K6CAQ3 |
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-糖 , 1種, 5分子
#4: 糖 | ChemComp-NAG / |
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-非ポリマー , 8種, 47分子
#3: 化合物 | ChemComp-GLY / #5: 化合物 | ChemComp-DD9 / #6: 化合物 | ChemComp-HP6 / #7: 化合物 | ChemComp-HEX / #8: 化合物 | ChemComp-UND / #9: 化合物 | ChemComp-NBU / #10: 化合物 | #11: 化合物 | |
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-詳細
研究の焦点であるリガンドがあるか | N |
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Has protein modification | Y |
-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: heteromeric glycine receptor subunit alpha-1 and beta, glycine-bound state1 (open state) タイプ: COMPLEX / Entity ID: #1-#2 / 由来: MULTIPLE SOURCES | ||||||||||||||||||||
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分子量 | 値: 0.24 MDa / 実験値: NO | ||||||||||||||||||||
由来(天然) |
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由来(組換発現) | 生物種: Homo sapiens (ヒト) | ||||||||||||||||||||
緩衝液 | pH: 8 | ||||||||||||||||||||
緩衝液成分 |
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試料 | 濃度: 6 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | ||||||||||||||||||||
試料支持 | グリッドの材料: GOLD / グリッドのタイプ: Quantifoil R1.2/1.3 | ||||||||||||||||||||
急速凍結 | 凍結剤: ETHANE / 湿度: 100 % |
-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 / 最大 デフォーカス(公称値): 2500 nm / 最小 デフォーカス(公称値): 1000 nm / アライメント法: BASIC |
試料ホルダ | 凍結剤: NITROGEN / 試料ホルダーモデル: GATAN LIQUID NITROGEN |
撮影 | 電子線照射量: 69.6 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
-解析
EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||
対称性 | 点対称性: C1 (非対称) | |||||||||||||||
3次元再構成 | 解像度: 3.63 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 21676 / 対称性のタイプ: POINT | |||||||||||||||
原子モデル構築 | 空間: REAL | |||||||||||||||
原子モデル構築 | PDB-ID: 7MLY Accession code: 7MLY / Source name: PDB / タイプ: experimental model |