+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-32095 | ||||||||||||||||||
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タイトル | Cryo-EM structure of human vasoactive intestinal polypeptide receptor 2 (VIP2R) in complex with PACAP27 and Gs | ||||||||||||||||||
マップデータ | |||||||||||||||||||
試料 |
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機能・相同性 | 機能・相同性情報 pituitary adenylate cyclase activating polypeptide activity / vasoactive intestinal polypeptide receptor activity / positive regulation of chemokine (C-C motif) ligand 5 production / positive regulation of growth hormone secretion / sensory perception of chemical stimulus / NGF-independant TRKA activation / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / D1 dopamine receptor binding / regulation of G protein-coupled receptor signaling pathway ...pituitary adenylate cyclase activating polypeptide activity / vasoactive intestinal polypeptide receptor activity / positive regulation of chemokine (C-C motif) ligand 5 production / positive regulation of growth hormone secretion / sensory perception of chemical stimulus / NGF-independant TRKA activation / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / D1 dopamine receptor binding / regulation of G protein-coupled receptor signaling pathway / neuropeptide hormone activity / G-protein activation / Activation of the phototransduction cascade / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / Ca2+ pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / G protein-coupled peptide receptor activity / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G alpha (z) signalling events / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / insulin secretion / Thrombin signalling through proteinase activated receptors (PARs) / G alpha (i) signalling events / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / alkylglycerophosphoethanolamine phosphodiesterase activity / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / beta-2 adrenergic receptor binding / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / peptide hormone receptor binding / G alpha (q) signalling events / photoreceptor outer segment membrane / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / spectrin binding / Vasopressin regulates renal water homeostasis via Aquaporins / activation of adenylate cyclase activity / adenylate cyclase-activating adrenergic receptor signaling pathway / adenylate cyclase activator activity / peptide hormone binding / negative regulation of cell cycle / neuropeptide signaling pathway / photoreceptor outer segment / positive regulation of protein kinase activity / cardiac muscle cell apoptotic process / insulin-like growth factor receptor binding / ionotropic glutamate receptor binding / photoreceptor inner segment / cAMP-mediated signaling / G-protein beta/gamma-subunit complex binding / positive regulation of GTPase activity / female pregnancy / G protein-coupled receptor activity / adenylate cyclase-activating G protein-coupled receptor signaling pathway / negative regulation of smooth muscle cell proliferation / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / Glucagon-type ligand receptors / cellular response to catecholamine stimulus / sensory perception of taste / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / neuron projection development / positive regulation of cold-induced thermogenesis / signaling receptor complex adaptor activity / cell-cell signaling / GTPase binding / regulation of protein localization / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / cellular response to hypoxia / cell body 類似検索 - 分子機能 | ||||||||||||||||||
生物種 | Bos taurus (ウシ) / Homo sapiens (ヒト) / synthetic construct (人工物) / Rattus norvegicus (ドブネズミ) | ||||||||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.74 Å | ||||||||||||||||||
データ登録者 | Xu YN / Feng WB / Zhou QT / Liang AY / Li J / Dai AT / Zhao FH / Yan JH / Chen CW / Li H ...Xu YN / Feng WB / Zhou QT / Liang AY / Li J / Dai AT / Zhao FH / Yan JH / Chen CW / Li H / Zhao LH / Xia T / Jiang Y / Xu HE / Yang DH / Wang MW | ||||||||||||||||||
資金援助 | 中国, 5件
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引用 | ジャーナル: Nat Commun / 年: 2022 タイトル: A distinctive ligand recognition mechanism by the human vasoactive intestinal polypeptide receptor 2. 著者: Yingna Xu / Wenbo Feng / Qingtong Zhou / Anyi Liang / Jie Li / Antao Dai / Fenghui Zhao / Jiahui Yan / Chuan-Wei Chen / Hao Li / Li-Hua Zhao / Tian Xia / Yi Jiang / H Eric Xu / Dehua Yang / Ming-Wei Wang / 要旨: Class B1 of G protein-coupled receptors (GPCRs) comprises 15 members activated by physiologically important peptide hormones. Among them, vasoactive intestinal polypeptide receptor 2 (VIP2R) is ...Class B1 of G protein-coupled receptors (GPCRs) comprises 15 members activated by physiologically important peptide hormones. Among them, vasoactive intestinal polypeptide receptor 2 (VIP2R) is expressed in the central and peripheral nervous systems and involved in a number of pathophysiological conditions, including pulmonary arterial hypertension, autoimmune and psychiatric disorders, in which it is thus a valuable drug target. Here, we report the cryo-electron microscopy structure of the human VIP2R bound to its endogenous ligand PACAP27 and the stimulatory G protein. Different from all reported peptide-bound class B1 GPCR structures, the N-terminal α-helix of VIP2R adopts a unique conformation that deeply inserts into a cleft between PACAP27 and the extracellular loop 1, thereby stabilizing the peptide-receptor interface. Its truncation or extension significantly decreased VIP2R-mediated cAMP accumulation. Our results provide additional information on peptide recognition and receptor activation among class B1 GPCRs and may facilitate the design of better therapeutics. | ||||||||||||||||||
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_32095.map.gz | 59.7 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-32095-v30.xml emd-32095.xml | 21.2 KB 21.2 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_32095.png | 16.9 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-32095 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-32095 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_32095_validation.pdf.gz | 435.9 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_32095_full_validation.pdf.gz | 435.4 KB | 表示 | |
XML形式データ | emd_32095_validation.xml.gz | 6.2 KB | 表示 | |
CIF形式データ | emd_32095_validation.cif.gz | 7 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32095 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32095 | HTTPS FTP |
-関連構造データ
関連構造データ | 7vqxMC 7wbjC 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 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-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_32095.map.gz / 形式: CCP4 / 大きさ: 64 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.071 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 : Cryo-EM structure of the human vasoactive intestinal polypeptide ...
+超分子 #1: Cryo-EM structure of the human vasoactive intestinal polypeptide ...
+超分子 #2: human vasoactive intestinal polypeptide receptor 2
+超分子 #3: Pituitary adenylate cyclase activating peptide-27
+超分子 #4: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
+超分子 #5: Guanine nucleotide-binding protein G(I) /G(S) /G(T) subunit beta-1
+超分子 #6: Guanine nucleotide-binding protein G(I) /G(S) /G(O) subunit gamma-2
+超分子 #7: Nanobody-35
+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: Pituitary adenylate cyclase-activating polypeptide 27
+分子 #5: Nanobody-35
+分子 #6: Vasoactive intestinal polypeptide receptor 2
-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
緩衝液 | pH: 7.4 |
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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 K3 (6k x 4k) / 平均電子線量: 80.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: OTHER |
電子光学系 | 照射モード: OTHER / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2.2 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 |
-画像解析
初期モデル | モデルのタイプ: PDB ENTRY PDBモデル - PDB ID: |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 2.74 Å / 解像度の算出法: DIFFRACTION PATTERN/LAYERLINES / 使用した粒子像数: 602466 |
初期 角度割当 | タイプ: OTHER |
最終 角度割当 | タイプ: OTHER |