+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7f9y | |||||||||
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タイトル | ghrelin-bound ghrelin receptor in complex with Gq | |||||||||
要素 |
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キーワード | MEMBRANE PROTEIN (膜タンパク質) / ghrelin (グレリン) / GPCR (Gタンパク質共役受容体) / Gq | |||||||||
機能・相同性 | 機能・相同性情報 ghrelin receptor binding / positive regulation of bone development / positive regulation of gastric mucosal blood circulation / negative regulation of locomotion / cortisol secretion / positive regulation of small intestinal transit / growth hormone-releasing hormone activity / negative regulation of circadian sleep/wake cycle, REM sleep / positive regulation of circadian sleep/wake cycle, non-REM sleep / regulation of response to food ...ghrelin receptor binding / positive regulation of bone development / positive regulation of gastric mucosal blood circulation / negative regulation of locomotion / cortisol secretion / positive regulation of small intestinal transit / growth hormone-releasing hormone activity / negative regulation of circadian sleep/wake cycle, REM sleep / positive regulation of circadian sleep/wake cycle, non-REM sleep / regulation of response to food / regulation of gastric motility / regulation of transmission of nerve impulse / gastric acid secretion / positive regulation of corticotropin secretion / positive regulation of cortisol secretion / growth hormone secretion / positive regulation of growth rate / positive regulation of eating behavior / positive regulation of appetite / positive regulation of small intestine smooth muscle contraction / adult feeding behavior / positive regulation of growth hormone secretion / positive regulation of growth hormone receptor signaling pathway / positive regulation of multicellular organism growth / actin polymerization or depolymerization / positive regulation of synapse assembly / cartilage development / regulation of postsynapse organization / positive regulation of vascular endothelial cell proliferation / negative regulation of interleukin-1 beta production / postsynaptic modulation of chemical synaptic transmission / protein tyrosine kinase activator activity / positive regulation of sprouting angiogenesis / dendrite development / negative regulation of endothelial cell proliferation / positive regulation of insulin secretion involved in cellular response to glucose stimulus / negative regulation of interleukin-6 production / decidualization / negative regulation of tumor necrosis factor production / negative regulation of insulin secretion / Synthesis, secretion, and deacylation of Ghrelin / response to electrical stimulus / synapse assembly / excitatory postsynaptic potential / positive regulation of adipose tissue development / hormone-mediated signaling pathway / Peptide ligand-binding receptors / response to hormone / negative regulation of angiogenesis / G protein-coupled receptor binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / Schaffer collateral - CA1 synapse / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G-protein activation / 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 / positive regulation of insulin secretion / 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 / negative regulation of inflammatory response / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / adenylate cyclase-activating dopamine receptor signaling pathway / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / response to estrogen / sensory perception of taste / GPER1 signaling / G-protein beta-subunit binding / glucose metabolic process / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / retina development in camera-type eye / GTPase binding / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cold-induced thermogenesis / regulation of cell population proliferation / G alpha (i) signalling events 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) Lama glama (ラマ) | |||||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.9 Å | |||||||||
データ登録者 | Wang, Y. / Zhuang, Y. / Xu, P. / Xu, H.E. / Jiang, Y. | |||||||||
資金援助 | 中国, 1件
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引用 | ジャーナル: Nat Commun / 年: 2021 タイトル: Molecular recognition of an acyl-peptide hormone and activation of ghrelin receptor. 著者: Yue Wang / Shimeng Guo / Youwen Zhuang / Ying Yun / Peiyu Xu / Xinheng He / Jia Guo / Wanchao Yin / H Eric Xu / Xin Xie / Yi Jiang / 要旨: Ghrelin, also called "the hunger hormone", is a gastric peptide hormone that regulates food intake, body weight, as well as taste sensation, reward, cognition, learning and memory. One unique feature ...Ghrelin, also called "the hunger hormone", is a gastric peptide hormone that regulates food intake, body weight, as well as taste sensation, reward, cognition, learning and memory. One unique feature of ghrelin is its acylation, primarily with an octanoic acid, which is essential for its binding and activation of the ghrelin receptor, a G protein-coupled receptor. The multifaceted roles of ghrelin make ghrelin receptor a highly attractive drug target for growth retardation, obesity, and metabolic disorders. Here we present two cryo-electron microscopy structures of G-coupled ghrelin receptor bound to ghrelin and a synthetic agonist, GHRP-6. Analysis of these two structures reveals a unique binding pocket for the octanoyl group, which guides the correct positioning of the peptide to initiate the receptor activation. Together with mutational and functional data, our structures define the rules for recognition of the acylated peptide hormone and activation of ghrelin receptor, and provide structural templates to facilitate drug design targeting ghrelin receptor. | |||||||||
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 | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7f9y.cif.gz | 225.2 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7f9y.ent.gz | 176.1 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7f9y.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/f9/7f9y ftp://data.pdbj.org/pub/pdb/validation_reports/f9/7f9y | HTTPS FTP |
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-関連構造データ
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
-タンパク質 , 2種, 2分子 AR
#1: タンパク質 | 分子量: 41855.578 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) |
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#6: タンパク質 | 分子量: 74282.609 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: cybC 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) |
-Guanine nucleotide-binding protein ... , 2種, 2分子 BG
#2: タンパク質 | 分子量: 40226.992 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNB1 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P62873 |
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#4: タンパク質 | 分子量: 7861.143 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNG2 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P59768 |
-タンパク質・ペプチド / 抗体 , 2種, 2分子 CN
#3: タンパク質・ペプチド | 分子量: 3252.726 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GHRL, MTLRP, UNQ524/PRO1066 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q9UBU3 |
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#5: 抗体 | 分子量: 15343.019 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Lama glama (ラマ) / 発現宿主: Escherichia coli (大腸菌) |
-非ポリマー , 2種, 3分子
#7: 化合物 | ChemComp-OCA / |
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#8: 化合物 |
-詳細
研究の焦点であるリガンドがあるか | Y |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-試料調製
構成要素 | 名称: ghrelin-bound ghrelin receptor in complex with Gq / タイプ: COMPLEX / Entity ID: #1-#6 / 由来: RECOMBINANT |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
緩衝液 | pH: 7.4 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: OTHER |
電子レンズ | モード: OTHER / 最大 デフォーカス(公称値): 3000 nm / 最小 デフォーカス(公称値): 500 nm |
撮影 | 電子線照射量: 80 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
-解析
CTF補正 | タイプ: NONE |
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3次元再構成 | 解像度: 2.9 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 522055 / 対称性のタイプ: POINT |