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基本情報
登録情報 | ![]() | ||||||||||||||||||
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タイトル | Cryo-EM structure of human full-length extrasynaptic alpha4beta3delta GABA(A)R in complex with GABA, histamine and nanobody Nb25 | ||||||||||||||||||
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![]() | pentameric ligand-gated ion channel / neurotransmitter receptor / GABA receptor / MEMBRANE PROTEIN | ||||||||||||||||||
機能・相同性 | ![]() benzodiazepine receptor activity / cellular response to histamine / GABA receptor activation / GABA-A receptor activity / GABA-gated chloride ion channel activity / GABA-A receptor complex / inhibitory synapse assembly / Signaling by ERBB4 / synaptic transmission, GABAergic / gamma-aminobutyric acid signaling pathway ...benzodiazepine receptor activity / cellular response to histamine / GABA receptor activation / GABA-A receptor activity / GABA-gated chloride ion channel activity / GABA-A receptor complex / inhibitory synapse assembly / Signaling by ERBB4 / synaptic transmission, GABAergic / gamma-aminobutyric acid signaling pathway / postsynaptic specialization membrane / neurotransmitter receptor activity / chloride channel activity / roof of mouth development / chloride channel complex / transmembrane transporter complex / GABA-ergic synapse / regulation of postsynaptic membrane potential / chloride transmembrane transport / dendrite membrane / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / cytoplasmic vesicle membrane / postsynaptic membrane / postsynapse / neuron projection / axon / neuronal cell body / synapse / dendrite / signal transduction / identical protein binding / plasma membrane 類似検索 - 分子機能 | ||||||||||||||||||
生物種 | ![]() | ||||||||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.0 Å | ||||||||||||||||||
![]() | Sente A / Desai R | ||||||||||||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Differential assembly diversifies GABA receptor structures and signalling. 著者: Andrija Sente / Rooma Desai / Katerina Naydenova / Tomas Malinauskas / Youssef Jounaidi / Jonas Miehling / Xiaojuan Zhou / Simonas Masiulis / Steven W Hardwick / Dimitri Y Chirgadze / Keith W ...著者: Andrija Sente / Rooma Desai / Katerina Naydenova / Tomas Malinauskas / Youssef Jounaidi / Jonas Miehling / Xiaojuan Zhou / Simonas Masiulis / Steven W Hardwick / Dimitri Y Chirgadze / Keith W Miller / A Radu Aricescu / ![]() ![]() ![]() 要旨: Type A γ-aminobutyric acid receptors (GABARs) are pentameric ligand-gated chloride channels that mediate fast inhibitory signalling in neural circuits and can be modulated by essential medicines ...Type A γ-aminobutyric acid receptors (GABARs) are pentameric ligand-gated chloride channels that mediate fast inhibitory signalling in neural circuits and can be modulated by essential medicines including general anaesthetics and benzodiazepines. Human GABAR subunits are encoded by 19 paralogous genes that can, in theory, give rise to 495,235 receptor types. However, the principles that govern the formation of pentamers, the permutational landscape of receptors that may emerge from a subunit set and the effect that this has on GABAergic signalling remain largely unknown. Here we use cryogenic electron microscopy to determine the structures of extrasynaptic GABARs assembled from α4, β3 and δ subunits, and their counterparts incorporating γ2 instead of δ subunits. In each case, we identified two receptor subtypes with distinct stoichiometries and arrangements, all four differing from those previously observed for synaptic, α1-containing receptors. This, in turn, affects receptor responses to physiological and synthetic modulators by creating or eliminating ligand-binding sites at subunit interfaces. We provide structural and functional evidence that selected GABAR arrangements can act as coincidence detectors, simultaneously responding to two neurotransmitters: GABA and histamine. Using assembly simulations and single-cell RNA sequencing data, we calculated the upper bounds for receptor diversity in recombinant systems and in vivo. We propose that differential assembly is a pervasive mechanism for regulating the physiology and pharmacology of GABARs. | ||||||||||||||||||
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構造の表示
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マップデータ | ![]() | 77.2 MB | ![]() | |
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画像 | ![]() | 72.7 KB | ||
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-検証レポート
文書・要旨 | ![]() | 522.9 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 522.5 KB | 表示 | |
XML形式データ | ![]() | 6.4 KB | 表示 | |
CIF形式データ | ![]() | 7.3 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 | ![]() 7qn7MC ![]() 7qn5C ![]() 7qn6C ![]() 7qn8C ![]() 7qn9C ![]() 7qnaC ![]() 7qnbC ![]() 7qncC ![]() 7qndC ![]() 7qneC M: このマップから作成された原子モデル 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 ![]() |
電子顕微鏡画像生データ | ![]() Data size: 2.8 TB Data #1: Unaligned multi-frame micrographs of GABA(A)Rs purified from cells epxressing human full-length alpha4, beta3 and delta subunits, in presence of GABA, histamine, Ro15-4513 and nanobody Nb25 ...Data #1: Unaligned multi-frame micrographs of GABA(A)Rs purified from cells epxressing human full-length alpha4, beta3 and delta subunits, in presence of GABA, histamine, Ro15-4513 and nanobody Nb25 [micrographs - multiframe]) ![]() Data size: 3.0 TB Data #1: Unaligned multi-frame micrographs of GABA(A) receptors purified from cells expressing human full-length alpha4, beta3 and delta subunits, in presence of GABA, histamine and nanobody Nb25 ...Data #1: Unaligned multi-frame micrographs of GABA(A) receptors purified from cells expressing human full-length alpha4, beta3 and delta subunits, in presence of GABA, histamine and nanobody Nb25 [micrographs - multiframe]) |
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リンク
EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 0.896 Å | ||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
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試料の構成要素
+全体 : Human full-length extrasynaptic alpha4beta3delta GABA(A)R in comp...
+超分子 #1: Human full-length extrasynaptic alpha4beta3delta GABA(A)R in comp...
+分子 #1: Gamma-aminobutyric acid receptor subunit alpha-4
+分子 #2: Gamma-aminobutyric acid receptor subunit beta-3
+分子 #3: Gamma-aminobutyric acid receptor subunit delta
+分子 #4: Nanobody Nb25
+分子 #7: 1,2-DIPALMITOYL-SN-GLYCERO-3-PHOSPHATE
+分子 #8: DECANE
+分子 #9: 2-acetamido-2-deoxy-beta-D-glucopyranose
+分子 #10: GAMMA-AMINO-BUTANOIC ACID
+分子 #11: HEXADECANE
+分子 #12: HISTAMINE
+分子 #13: water
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
緩衝液 | pH: 7.6 構成要素:
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凍結 | 凍結剤: ETHANE / チャンバー内湿度: 95 % / チャンバー内温度: 287 K / 装置: LEICA PLUNGER |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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特殊光学系 | エネルギーフィルター - 名称: GIF Bioquantum / エネルギーフィルター - スリット幅: 20 eV |
撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 平均電子線量: 40.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | C2レンズ絞り径: 50.0 µm / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm / 最大 デフォーカス(公称値): 2.1 µm 最小 デフォーカス(公称値): 0.7000000000000001 µm 倍率(公称値): 130000 |
試料ステージ | ホルダー冷却材: NITROGEN |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
-原子モデル構築 1
精密化 | プロトコル: AB INITIO MODEL |
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得られたモデル | ![]() PDB-7qn7: |