+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-30003 | ||||||||||||||||||
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タイトル | Cryo-EM map of CRF1 receptor bound to CRF and Gs protein | ||||||||||||||||||
マップデータ | Sharpened map | ||||||||||||||||||
試料 |
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機能・相同性 | 機能・相同性情報 regulation of adenylate cyclase activity involved in G protein-coupled receptor signaling pathway / corticotropin-releasing hormone binding / regulation of corticosterone secretion / corticotrophin-releasing factor receptor activity / corticotropin-releasing hormone receptor activity / corticotropin secretion / general adaptation syndrome, behavioral process / parturition / cellular response to corticotropin-releasing hormone stimulus / negative regulation of voltage-gated calcium channel activity ...regulation of adenylate cyclase activity involved in G protein-coupled receptor signaling pathway / corticotropin-releasing hormone binding / regulation of corticosterone secretion / corticotrophin-releasing factor receptor activity / corticotropin-releasing hormone receptor activity / corticotropin secretion / general adaptation syndrome, behavioral process / parturition / cellular response to corticotropin-releasing hormone stimulus / negative regulation of voltage-gated calcium channel activity / behavioral response to ethanol / fear response / G protein-coupled peptide receptor activity / Class B/2 (Secretin family receptors) / exploration behavior / adrenal gland development / PKA activation in glucagon signalling / hair follicle placode formation / mu-type opioid receptor binding / developmental growth / corticotropin-releasing hormone receptor 1 binding / intracellular transport / D1 dopamine receptor binding / Hedgehog 'off' state / beta-2 adrenergic receptor binding / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / adenylate cyclase activator activity / trans-Golgi network membrane / female pregnancy / ionotropic glutamate receptor binding / insulin-like growth factor receptor binding / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / bone development / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G-protein activation / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / cognition / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / platelet aggregation / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / sensory perception of smell / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / positive regulation of cold-induced thermogenesis / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell surface receptor signaling pathway / endosome / neuron projection / immune response / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / protein-containing complex binding / GTP binding / signal transduction / extracellular exosome 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 | Liang YL / Belousoff MJ / Zhao P / Danev R / Sexton PM / Wootten D | ||||||||||||||||||
資金援助 | オーストラリア, 日本, 5件
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引用 | ジャーナル: Mol Cell / 年: 2020 タイトル: Toward a Structural Understanding of Class B GPCR Peptide Binding and Activation. 著者: Yi-Lynn Liang / Matthew J Belousoff / Peishen Zhao / Cassandra Koole / Madeleine M Fletcher / Tin T Truong / Villy Julita / George Christopoulos / H Eric Xu / Yan Zhang / Maryam Khoshouei / ...著者: Yi-Lynn Liang / Matthew J Belousoff / Peishen Zhao / Cassandra Koole / Madeleine M Fletcher / Tin T Truong / Villy Julita / George Christopoulos / H Eric Xu / Yan Zhang / Maryam Khoshouei / Arthur Christopoulos / Radostin Danev / Patrick M Sexton / Denise Wootten / 要旨: Class B G protein-coupled receptors (GPCRs) are important therapeutic targets for major diseases. Here, we present structures of peptide and Gs-bound pituitary adenylate cyclase-activating peptide, ...Class B G protein-coupled receptors (GPCRs) are important therapeutic targets for major diseases. Here, we present structures of peptide and Gs-bound pituitary adenylate cyclase-activating peptide, PAC1 receptor, and corticotropin-releasing factor (CRF), (CRF1) receptor. Together with recently solved structures, these provide coverage of the major class B GPCR subfamilies. Diverse orientations of the extracellular domain to the receptor core in different receptors are at least partially dependent on evolutionary conservation in the structure and nature of peptide interactions. Differences in peptide interactions to the receptor core also influence the interlinked TM2-TM1-TM6/ECL3/TM7 domain, and this is likely important in their diverse signaling. However, common conformational reorganization of ECL2, linked to reorganization of ICL2, modulates G protein contacts. Comparison between receptors reveals ICL2 as a key domain forming dynamic G protein interactions in a receptor- and ligand-specific manner. This work advances our understanding of class B GPCR activation and Gs coupling. | ||||||||||||||||||
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 | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_30003.map.gz | 19.4 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-30003-v30.xml emd-30003.xml | 19.3 KB 19.3 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_30003.png | 130.5 KB | ||
マスクデータ | emd_30003_msk_1.map | 20.8 MB | マスクマップ | |
その他 | emd_30003_additional.map.gz emd_30003_additional_1.map.gz emd_30003_half_map_1.map.gz emd_30003_half_map_2.map.gz | 15.8 MB 15.8 MB 15.8 MB 15.8 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-30003 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-30003 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_30003_validation.pdf.gz | 79.6 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_30003_full_validation.pdf.gz | 78.7 KB | 表示 | |
XML形式データ | emd_30003_validation.xml.gz | 493 B | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30003 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30003 | HTTPS FTP |
-関連構造データ
関連構造データ | 0993C 6p9xC 6p9yC C: 同じ文献を引用 (文献) |
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類似構造データ | |
電子顕微鏡画像生データ | EMPIAR-10361 (タイトル: Cryo-EM of CRF1 receptor bound to CRF and Gs protein Data size: 2.6 TB Data #1: Unaligned multi-frame gain-normalized movies in LZW compressed TIFF format [micrographs - multiframe]) |
-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_30003.map.gz / 形式: CCP4 / 大きさ: 20.8 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Sharpened map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.207 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-マスク #1
ファイル | emd_30003_msk_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-追加マップ: Unsharpened map
ファイル | emd_30003_additional.map | ||||||||||||
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注釈 | Unsharpened map | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: Unsharpened map
ファイル | emd_30003_additional_1.map | ||||||||||||
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注釈 | Unsharpened map | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: Unsharpened half-map 2
ファイル | emd_30003_half_map_1.map | ||||||||||||
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注釈 | Unsharpened half-map 2 | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: Unsharpened half-map 1
ファイル | emd_30003_half_map_2.map | ||||||||||||
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注釈 | Unsharpened half-map 1 | ||||||||||||
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 : CRF1 receptor bound to CRF and Gs protein
全体 | 名称: CRF1 receptor bound to CRF and Gs protein |
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要素 |
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-超分子 #1: CRF1 receptor bound to CRF and Gs protein
超分子 | 名称: CRF1 receptor bound to CRF and Gs protein / タイプ: complex / ID: 1 / 親要素: 0 |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
分子量 | 理論値: 150 kDa/nm |
-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 | 4.35 mg/mL |
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緩衝液 | pH: 7.4 |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 277 K / 装置: FEI VITROBOT MARK IV / 詳細: blot time 10 s. |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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特殊光学系 | 位相板: VOLTA PHASE PLATE / エネルギーフィルター - 名称: GIF Quantum LS / エネルギーフィルター - スリット幅: 25 eV |
撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 撮影したグリッド数: 1 / 実像数: 4300 / 平均露光時間: 3.715 sec. / 平均電子線量: 64.0 e/Å2 詳細: Volta phase plate images: 3274; Conventional defocus images: 1026 |
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: 50.0 µm / 最大 デフォーカス(補正後): 1.6 µm / 最小 デフォーカス(補正後): 0.4 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): 1.6 µm / 最小 デフォーカス(公称値): 0.4 µm / 倍率(公称値): 105000 |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |