+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-25401 | |||||||||
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タイトル | 5-HT2B receptor bound to LSD obtained by cryo-electron microscopy (cryoEM) | |||||||||
マップデータ | Cryo-EM map for 5-HT2BR bound to LSD | |||||||||
試料 |
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機能・相同性 | 機能・相同性情報 intestine smooth muscle contraction / Gq/11-coupled serotonin receptor activity / phospholipase C-activating serotonin receptor signaling pathway / positive regulation of phosphatidylinositol biosynthetic process / G protein-coupled serotonin receptor signaling pathway / G protein-coupled serotonin receptor complex / protein kinase C signaling / regulation of behavior / Serotonin receptors / serotonin receptor signaling pathway ...intestine smooth muscle contraction / Gq/11-coupled serotonin receptor activity / phospholipase C-activating serotonin receptor signaling pathway / positive regulation of phosphatidylinositol biosynthetic process / G protein-coupled serotonin receptor signaling pathway / G protein-coupled serotonin receptor complex / protein kinase C signaling / regulation of behavior / Serotonin receptors / serotonin receptor signaling pathway / embryonic morphogenesis / cellular response to temperature stimulus / serotonin binding / vasoconstriction / G protein-coupled serotonin receptor activity / : / G protein-coupled receptor internalization / cardiac muscle hypertrophy / : / neural crest cell differentiation / neural crest cell migration / neurotransmitter receptor activity / cGMP-mediated signaling / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / positive regulation of cell division / G-protein alpha-subunit binding / heart morphogenesis / release of sequestered calcium ion into cytosol / positive regulation of endothelial cell proliferation / ERK1 and ERK2 cascade / phosphatidylinositol 3-kinase/protein kinase B signal transduction / phosphorylation / GTPase activator activity / positive regulation of MAP kinase activity / positive regulation of nitric-oxide synthase activity / positive regulation of cytokine production / calcium-mediated signaling / intracellular calcium ion homeostasis / positive regulation of canonical NF-kappaB signal transduction / G alpha (q) signalling events / chemical synaptic transmission / positive regulation of ERK1 and ERK2 cascade / response to xenobiotic stimulus / G protein-coupled receptor signaling pathway / positive regulation of cell population proliferation / synapse / dendrite / negative regulation of apoptotic process / nucleoplasm / plasma membrane / cytoplasm 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.7 Å | |||||||||
データ登録者 | Barros-Alvarez X / Cao C / Panova O / Roth BL / Skiniotis G | |||||||||
資金援助 | 1件
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引用 | ジャーナル: Neuron / 年: 2022 タイトル: Signaling snapshots of a serotonin receptor activated by the prototypical psychedelic LSD. 著者: Can Cao / Ximena Barros-Álvarez / Shicheng Zhang / Kuglae Kim / Marc A Dämgen / Ouliana Panova / Carl-Mikael Suomivuori / Jonathan F Fay / Xiaofang Zhong / Brian E Krumm / Ryan H Gumpper / ...著者: Can Cao / Ximena Barros-Álvarez / Shicheng Zhang / Kuglae Kim / Marc A Dämgen / Ouliana Panova / Carl-Mikael Suomivuori / Jonathan F Fay / Xiaofang Zhong / Brian E Krumm / Ryan H Gumpper / Alpay B Seven / Michael J Robertson / Nevan J Krogan / Ruth Hüttenhain / David E Nichols / Ron O Dror / Georgios Skiniotis / Bryan L Roth / 要旨: Serotonin (5-hydroxytryptamine [5-HT]) 5-HT2-family receptors represent essential targets for lysergic acid diethylamide (LSD) and all other psychedelic drugs. Although the primary psychedelic drug ...Serotonin (5-hydroxytryptamine [5-HT]) 5-HT2-family receptors represent essential targets for lysergic acid diethylamide (LSD) and all other psychedelic drugs. Although the primary psychedelic drug effects are mediated by the 5-HT serotonin receptor (HTR2A), the 5-HT serotonin receptor (HTR2B) has been used as a model receptor to study the activation mechanisms of psychedelic drugs due to its high expression and similarity to HTR2A. In this study, we determined the cryo-EM structures of LSD-bound HTR2B in the transducer-free, Gq-protein-coupled, and β-arrestin-1-coupled states. These structures provide distinct signaling snapshots of LSD's action, ranging from the transducer-free, partially active state to the transducer-coupled, fully active states. Insights from this study will both provide comprehensive molecular insights into the signaling mechanisms of the prototypical psychedelic LSD and accelerate the discovery of novel psychedelic drugs. | |||||||||
履歴 |
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-構造の表示
添付画像 |
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-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_25401.map.gz | 749.5 KB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-25401-v30.xml emd-25401.xml | 12.8 KB 12.8 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_25401.png | 110.4 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-25401 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-25401 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_25401_validation.pdf.gz | 295.3 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_25401_full_validation.pdf.gz | 294.9 KB | 表示 | |
XML形式データ | emd_25401_validation.xml.gz | 6.6 KB | 表示 | |
CIF形式データ | emd_25401_validation.cif.gz | 7.6 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-25401 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-25401 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_25401.map.gz / 形式: CCP4 / 大きさ: 178 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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注釈 | Cryo-EM map for 5-HT2BR bound to LSD | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.8677 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
-試料の構成要素
-全体 : 5-HT2B receptor bound to LSD
全体 | 名称: 5-HT2B receptor bound to LSD |
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要素 |
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-超分子 #1: 5-HT2B receptor bound to LSD
超分子 | 名称: 5-HT2B receptor bound to LSD / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1 |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
-分子 #1: 5-hydroxytryptamine receptor 2B
分子 | 名称: 5-hydroxytryptamine receptor 2B / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 35.052629 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: TESIPEEMKQ IVEEQGNKLH WAALLILMVI IPTIGGNTLV ILAVSLEKKL QYATNYFLMS LAVADLLVGL FVMPIALLTI MFEAMWPLP LVLCPAWLFL DVLFSTASIW HLCAISVDRY IAIKKPIQAN QYNSRATAFI KITVVWLISI GIAIPVPIKG I ETDVDNPN ...文字列: TESIPEEMKQ IVEEQGNKLH WAALLILMVI IPTIGGNTLV ILAVSLEKKL QYATNYFLMS LAVADLLVGL FVMPIALLTI MFEAMWPLP LVLCPAWLFL DVLFSTASIW HLCAISVDRY IAIKKPIQAN QYNSRATAFI KITVVWLISI GIAIPVPIKG I ETDVDNPN NITCVLTKER FGDFMLFGSL AAFFTPLAIM IVTYFLTIHA LQKVRLLSGS RQTISNEQRA SKVLGIVFFL FL LMWCPFF ITNITLVLCD SCNQTTLQML LEIFVWIGYV SSGVNPLVYT LFNKTFRDAF GRYITCNYRA TKSV |
-分子 #2: 2-acetamido-2-deoxy-beta-D-glucopyranose
分子 | 名称: 2-acetamido-2-deoxy-beta-D-glucopyranose / タイプ: ligand / ID: 2 / コピー数: 1 / 式: NAG |
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分子量 | 理論値: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-分子 #3: (8alpha)-N,N-diethyl-6-methyl-9,10-didehydroergoline-8-carboxamide
分子 | 名称: (8alpha)-N,N-diethyl-6-methyl-9,10-didehydroergoline-8-carboxamide タイプ: ligand / ID: 3 / コピー数: 1 / 式: 7LD |
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分子量 | 理論値: 323.432 Da |
Chemical component information | ChemComp-7LD: |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
濃度 | 6.5 mg/mL |
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緩衝液 | pH: 7.5 |
グリッド | モデル: UltrAuFoil R1.2/1.3 |
凍結 | 凍結剤: ETHANE / 装置: FEI VITROBOT MARK IV |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 平均電子線量: 1.23 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | C2レンズ絞り径: 70.0 µm / 倍率(補正後): 55000 / 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): 1.8 µm / 最小 デフォーカス(公称値): 0.8 µm |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |