+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-21683 | |||||||||||||||
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タイトル | Human secretin receptor Gs complex | |||||||||||||||
マップデータ | Postprocessed MAP | |||||||||||||||
試料 |
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機能・相同性 | 機能・相同性情報 secretin receptor activity / digestive hormone activity / positive regulation of somatostatin secretion / negative regulation of gastrin-induced gastric acid secretion / positive regulation of pancreatic juice secretion / regulation of appetite / pancreatic juice secretion / intracellular water homeostasis / positive regulation of lipid catabolic process / positive regulation of cAMP-mediated signaling ...secretin receptor activity / digestive hormone activity / positive regulation of somatostatin secretion / negative regulation of gastrin-induced gastric acid secretion / positive regulation of pancreatic juice secretion / regulation of appetite / pancreatic juice secretion / intracellular water homeostasis / positive regulation of lipid catabolic process / positive regulation of cAMP-mediated signaling / embryonic digestive tract development / G protein-coupled peptide receptor activity / cytoplasmic microtubule / diet induced thermogenesis / peptide hormone binding / PKA activation in glucagon signalling / hair follicle placode formation / developmental growth / D1 dopamine receptor binding / intracellular transport / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / adenylate cyclase activator activity / response to nutrient levels / trans-Golgi network membrane / G protein-coupled receptor binding / hippocampus development / G-protein beta/gamma-subunit complex binding / bone development / Olfactory Signaling Pathway / brain development / Activation of the phototransduction cascade / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / regulation of synaptic plasticity / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / hormone activity / 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 / platelet aggregation / 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 / 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 / Ca2+ pathway / positive regulation of cold-induced thermogenesis / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell population proliferation / cell surface receptor signaling pathway / G protein-coupled receptor signaling pathway / lysosomal membrane / signaling receptor binding / GTPase activity / synapse / protein-containing complex binding / GTP binding / signal transduction / extracellular space / extracellular exosome / extracellular region 類似検索 - 分子機能 | |||||||||||||||
生物種 | Homo sapiens (ヒト) / Lama glama (ラマ) | |||||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 4.3 Å | |||||||||||||||
データ登録者 | Belousoff MJ / Khoshouei M | |||||||||||||||
資金援助 | 米国, オーストラリア, 英国, 4件
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引用 | ジャーナル: Nat Commun / 年: 2020 タイトル: Structure and dynamics of the active Gs-coupled human secretin receptor. 著者: Maoqing Dong / Giuseppe Deganutti / Sarah J Piper / Yi-Lynn Liang / Maryam Khoshouei / Matthew J Belousoff / Kaleeckal G Harikumar / Christopher A Reynolds / Alisa Glukhova / Sebastian G B ...著者: Maoqing Dong / Giuseppe Deganutti / Sarah J Piper / Yi-Lynn Liang / Maryam Khoshouei / Matthew J Belousoff / Kaleeckal G Harikumar / Christopher A Reynolds / Alisa Glukhova / Sebastian G B Furness / Arthur Christopoulos / Radostin Danev / Denise Wootten / Patrick M Sexton / Laurence J Miller / 要旨: The class B secretin GPCR (SecR) has broad physiological effects, with target potential for treatment of metabolic and cardiovascular disease. Molecular understanding of SecR binding and activation ...The class B secretin GPCR (SecR) has broad physiological effects, with target potential for treatment of metabolic and cardiovascular disease. Molecular understanding of SecR binding and activation is important for its therapeutic exploitation. We combined cryo-electron microscopy, molecular dynamics, and biochemical cross-linking to determine a 2.3 Å structure, and interrogate dynamics, of secretin bound to the SecR:Gs complex. SecR exhibited a unique organization of its extracellular domain (ECD) relative to its 7-transmembrane (TM) core, forming more extended interactions than other family members. Numerous polar interactions formed between secretin and the receptor extracellular loops (ECLs) and TM helices. Cysteine-cross-linking, cryo-electron microscopy multivariate analysis and molecular dynamics simulations revealed that interactions between peptide and receptor were dynamic, and suggested a model for initial peptide engagement where early interactions between the far N-terminus of the peptide and SecR ECL2 likely occur following initial binding of the peptide C-terminus to the ECD. | |||||||||||||||
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_21683.map.gz | 5 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-21683-v30.xml emd-21683.xml | 23 KB 23 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_21683_fsc.xml | 7.9 KB | 表示 | FSCデータファイル |
画像 | emd_21683.png | 41.9 KB | ||
マスクデータ | emd_21683_msk_1.map | 40.6 MB | マスクマップ | |
その他 | emd_21683_half_map_1.map.gz emd_21683_half_map_2.map.gz | 31.3 MB 31.2 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-21683 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-21683 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_21683_validation.pdf.gz | 541.5 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_21683_full_validation.pdf.gz | 541.1 KB | 表示 | |
XML形式データ | emd_21683_validation.xml.gz | 13.5 KB | 表示 | |
CIF形式データ | emd_21683_validation.cif.gz | 19.2 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-21683 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-21683 | 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_21683.map.gz / 形式: CCP4 / 大きさ: 40.6 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Postprocessed MAP | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.86 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_21683_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 |
-ハーフマップ: half map 1
ファイル | emd_21683_half_map_1.map | ||||||||||||
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注釈 | half map 1 | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: half map 2
ファイル | emd_21683_half_map_2.map | ||||||||||||
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注釈 | half map 2 | ||||||||||||
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 : Gs coupled sectretin complex with secretin peptide
+超分子 #1: Gs coupled sectretin complex with secretin peptide
+超分子 #2: Guanine nucleotide-binding protein G(s) subunit alpha isoforms sh...
+超分子 #3: Nanobody35
+超分子 #4: Secretin
+分子 #1: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
+分子 #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+分子 #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+分子 #4: Nanobody35
+分子 #5: Secretin
+分子 #6: Secretin receptor
-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 | 1.5 mg/mL |
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緩衝液 | pH: 7.4 |
凍結 | 凍結剤: ETHANE |
-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 K2 SUMMIT (4k x 4k) 検出モード: COUNTING / 平均電子線量: 46.0 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 |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |