+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-20278 | ||||||||||||||||||||||||||||||
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タイトル | PAC1 GPCR Receptor complex | ||||||||||||||||||||||||||||||
マップデータ | post-processed map | ||||||||||||||||||||||||||||||
試料 |
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機能・相同性 | 機能・相同性情報 negative regulation of response to reactive oxygen species / development of primary female sexual characteristics / pituitary adenylate cyclase activating polypeptide activity / vasoactive intestinal polypeptide receptor activity / positive regulation of growth hormone secretion / positive regulation of chemokine (C-C motif) ligand 5 production / positive regulation of cAMP-mediated signaling / NGF-independant TRKA activation / regulation of G protein-coupled receptor signaling pathway / neuropeptide hormone activity ...negative regulation of response to reactive oxygen species / development of primary female sexual characteristics / pituitary adenylate cyclase activating polypeptide activity / vasoactive intestinal polypeptide receptor activity / positive regulation of growth hormone secretion / positive regulation of chemokine (C-C motif) ligand 5 production / positive regulation of cAMP-mediated signaling / NGF-independant TRKA activation / regulation of G protein-coupled receptor signaling pathway / neuropeptide hormone activity / neuropeptide binding / G protein-coupled peptide receptor activity / positive regulation of small GTPase mediated signal transduction / insulin secretion / positive regulation of inositol phosphate biosynthetic process / peptide hormone receptor binding / positive regulation of calcium ion transport into cytosol / peptide hormone binding / PKA activation in glucagon signalling / hair follicle placode formation / adenylate cyclase binding / negative regulation of cell cycle / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / developmental growth / D1 dopamine receptor binding / intracellular transport / bicellular tight junction / positive regulation of protein kinase activity / neuropeptide signaling pathway / Hedgehog 'off' state / multicellular organismal response to stress / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / beta-2 adrenergic receptor binding / adenylate cyclase activator activity / cAMP-mediated signaling / positive regulation of GTPase activity / trans-Golgi network membrane / caveola / female pregnancy / insulin-like growth factor receptor binding / ionotropic glutamate receptor binding / G-protein beta/gamma-subunit complex binding / bone development / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / 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 / 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) / small GTPase binding / Sensory perception of sweet, bitter, and umami (glutamate) taste / platelet aggregation / 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 / regulation of protein localization / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / neuron projection development / 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 / response to estradiol / cell-cell signaling / retina development in camera-type eye / Ca2+ pathway / signaling receptor activity / positive regulation of cold-induced thermogenesis / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration 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: 3.01 Å | ||||||||||||||||||||||||||||||
データ登録者 | Belousoff MJ / Liang YL / Sexton P / Danev R | ||||||||||||||||||||||||||||||
資金援助 | オーストラリア, 日本, 9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_20278.map.gz | 8.1 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-20278-v30.xml emd-20278.xml | 26.9 KB 26.9 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_20278_fsc.xml | 10.3 KB | 表示 | FSCデータファイル |
画像 | emd_20278.png | 40.6 KB | ||
マスクデータ | emd_20278_msk_1.map | 91.1 MB | マスクマップ | |
その他 | emd_20278_additional.map.gz emd_20278_half_map_1.map.gz emd_20278_half_map_2.map.gz | 59.2 MB 71.3 MB 71.3 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-20278 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-20278 | HTTPS FTP |
-関連構造データ
関連構造データ | 6p9yMC 0993C 6p9xC 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 | |
電子顕微鏡画像生データ | EMPIAR-10359 (タイトル: Cryo-EM of PAC1 receptor bound to PACAP38 and Gs protein Data size: 4.8 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_20278.map.gz / 形式: CCP4 / 大きさ: 91.1 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | post-processed map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.826 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_20278_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: local resolution filtered map
ファイル | emd_20278_additional.map | ||||||||||||
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注釈 | local resolution filtered 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: half-map 2
ファイル | emd_20278_half_map_1.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 |
-ハーフマップ: half-map 1
ファイル | emd_20278_half_map_2.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 |
-試料の構成要素
+全体 : Complex of active-state Pituitary adenylate cyclase-activating po...
+超分子 #1: Complex of active-state Pituitary adenylate cyclase-activating po...
+超分子 #2: Guanine nucleotide-binding protein G(s) subunit alpha isoforms sh...
+超分子 #3: Nanobody 35
+超分子 #4: Pituitary adenylate cyclase-activating polypeptide type I receptor
+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: Nanobody 35
+分子 #5: Pituitary adenylate cyclase-activating polypeptide
+分子 #6: Pituitary adenylate cyclase-activating polypeptide type I 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
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) / 撮影したグリッド数: 1 / 平均露光時間: 3.7 sec. / 平均電子線量: 1.03 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: SPOT SCAN / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |