+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-36342 | |||||||||
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タイトル | Cryo-EM structure of the beta2AR-mBRIL/1b3 Fab/Glue complex with a partial agonist | |||||||||
マップデータ | ||||||||||
試料 |
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キーワード | complex / chimera / GPCR / membrane protein | |||||||||
機能・相同性 | 機能・相同性情報 beta2-adrenergic receptor activity / positive regulation of mini excitatory postsynaptic potential / positive regulation of cAMP-dependent protein kinase activity / positive regulation of AMPA receptor activity / norepinephrine binding / Adrenoceptors / heat generation / positive regulation of autophagosome maturation / norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure / activation of transmembrane receptor protein tyrosine kinase activity ...beta2-adrenergic receptor activity / positive regulation of mini excitatory postsynaptic potential / positive regulation of cAMP-dependent protein kinase activity / positive regulation of AMPA receptor activity / norepinephrine binding / Adrenoceptors / heat generation / positive regulation of autophagosome maturation / norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure / activation of transmembrane receptor protein tyrosine kinase activity / negative regulation of smooth muscle contraction / positive regulation of lipophagy / response to psychosocial stress / negative regulation of multicellular organism growth / negative regulation of G protein-coupled receptor signaling pathway / adrenergic receptor signaling pathway / endosome to lysosome transport / diet induced thermogenesis / neuronal dense core vesicle / positive regulation of protein kinase A signaling / adenylate cyclase binding / smooth muscle contraction / potassium channel regulator activity / bone resorption / positive regulation of bone mineralization / adenylate cyclase-activating adrenergic receptor signaling pathway / brown fat cell differentiation / regulation of sodium ion transport / response to cold / receptor-mediated endocytosis / electron transport chain / clathrin-coated endocytic vesicle membrane / positive regulation of protein serine/threonine kinase activity / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / cellular response to amyloid-beta / Cargo recognition for clathrin-mediated endocytosis / Clathrin-mediated endocytosis / positive regulation of cold-induced thermogenesis / amyloid-beta binding / G alpha (s) signalling events / transcription by RNA polymerase II / positive regulation of MAPK cascade / periplasmic space / electron transfer activity / early endosome / lysosome / cell surface receptor signaling pathway / receptor complex / endosome membrane / Ub-specific processing proteases / endosome / iron ion binding / apical plasma membrane / heme binding / protein-containing complex binding / Golgi apparatus / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / identical protein binding / membrane / nucleus / plasma membrane 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: 3.2 Å | |||||||||
データ登録者 | He BB / Zhong YX / Guo Q / Tao YY | |||||||||
資金援助 | 中国, 1件
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引用 | ジャーナル: Nat Chem Biol / 年: 2024 タイトル: A method for structure determination of GPCRs in various states. 著者: Qiong Guo / Binbin He / Yixuan Zhong / Haizhan Jiao / Yinhang Ren / Qinggong Wang / Qiangqiang Ge / Yongxiang Gao / Xiangyu Liu / Yang Du / Hongli Hu / Yuyong Tao / 要旨: G-protein-coupled receptors (GPCRs) are a class of integral membrane proteins that detect environmental cues and trigger cellular responses. Deciphering the functional states of GPCRs induced by ...G-protein-coupled receptors (GPCRs) are a class of integral membrane proteins that detect environmental cues and trigger cellular responses. Deciphering the functional states of GPCRs induced by various ligands has been one of the primary goals in the field. Here we developed an effective universal method for GPCR cryo-electron microscopy structure determination without the need to prepare GPCR-signaling protein complexes. Using this method, we successfully solved the structures of the β-adrenergic receptor (βAR) bound to antagonistic and agonistic ligands and the adhesion GPCR ADGRL3 in the apo state. For βAR, an intermediate state stabilized by the partial agonist was captured. For ADGRL3, the structure revealed that inactive ADGRL3 adopts a compact fold and that large unusual conformational changes on both the extracellular and intracellular sides are required for activation of adhesion GPCRs. We anticipate that this method will open a new avenue for understanding GPCR structure‒function relationships and drug development. | |||||||||
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_36342.map.gz | 79 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-36342-v30.xml emd-36342.xml | 14.3 KB 14.3 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_36342_fsc.xml | 9.2 KB | 表示 | FSCデータファイル |
画像 | emd_36342.png | 97.3 KB | ||
Filedesc metadata | emd-36342.cif.gz | 5.7 KB | ||
その他 | emd_36342_half_map_1.map.gz emd_36342_half_map_2.map.gz | 77.7 MB 77.7 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-36342 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36342 | 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_36342.map.gz / 形式: CCP4 / 大きさ: 83.7 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 1.07 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
-ハーフマップ: #2
ファイル | emd_36342_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_36342_half_map_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
-全体 : Cryo-EM structure of the beta2AR-mBRIL/1b3 Fab/Glue complex with ...
全体 | 名称: Cryo-EM structure of the beta2AR-mBRIL/1b3 Fab/Glue complex with a partial agonist |
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要素 |
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-超分子 #1: Cryo-EM structure of the beta2AR-mBRIL/1b3 Fab/Glue complex with ...
超分子 | 名称: Cryo-EM structure of the beta2AR-mBRIL/1b3 Fab/Glue complex with a partial agonist 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) |
-分子 #1: Beta-2 adrenergic receptor,Soluble cytochrome b562
分子 | 名称: Beta-2 adrenergic receptor,Soluble cytochrome b562 / 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: 51.594102 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MKTIIALSYI FCLVFADYKD DDDKDEVWVV GMGIVMSLIV LAIVFGNVLV ITAIAKFERL QTVTNYFITS LACADLVMGL AVVPFGAAH ILMKMWTFGN FWCEFWTSID VLCVTASIET LCVIAVDRYF AITSPFKYQS LLTKNKARVI ILMVWIVSGL T SFLPIQMH ...文字列: MKTIIALSYI FCLVFADYKD DDDKDEVWVV GMGIVMSLIV LAIVFGNVLV ITAIAKFERL QTVTNYFITS LACADLVMGL AVVPFGAAH ILMKMWTFGN FWCEFWTSID VLCVTASIET LCVIAVDRYF AITSPFKYQS LLTKNKARVI ILMVWIVSGL T SFLPIQMH WYRATHQEAI NCYAEETCCD FFTNQAYAIA SSIVSFYVPL VIMVFVYSRV FQEAKRQLAD LEDNWETLND NL KVIEKAD NAAQVKDALT KMRAAALDAQ KASGSGSPEM KDFRHGFDIL VGQIDDALKL ANEGKVKEAQ AAAEQLKTTR NAY IQKYLK FCLKEHKALK TLGIIMGTFT LCWLPFFIVN IVHVIQDNLI RKEVYILLNW IGYVNSGFNP LIYSRSPDFR IAFQ ELLKI AALKEKIAAL KEKIAALKEA EEKRASRLEE ELRRRLTEGS HHHHHHHH UniProtKB: Beta-2 adrenergic receptor, Soluble cytochrome b562, Beta-2 adrenergic receptor |
-分子 #2: ~{N}-[5-[(1~{R})-2-[[(2~{R})-1-(4-methoxyphenyl)propan-2-yl]amino...
分子 | 名称: ~{N}-[5-[(1~{R})-2-[[(2~{R})-1-(4-methoxyphenyl)propan-2-yl]amino]-1-oxidanyl-ethyl]-2-oxidanyl-phenyl]methanamide タイプ: ligand / ID: 2 / コピー数: 1 / 式: H98 |
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分子量 | 理論値: 344.405 Da |
Chemical component information | ChemComp-H98: |
-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 | cell |
-試料調製
緩衝液 | pH: 7.5 |
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グリッド | 材質: NICKEL/TITANIUM |
凍結 | 凍結剤: NITROGEN |
-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: 52.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 5.0 µm / 最小 デフォーカス(公称値): 1.2 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |