+
データを開く
-
基本情報
登録情報 | データベース: PDB / ID: 7w2z | ||||||
---|---|---|---|---|---|---|---|
タイトル | Cryo-EM structure of the ghrelin-bound human ghrelin receptor-Go complex | ||||||
![]() |
| ||||||
![]() | SIGNALING PROTEIN / GPCR / Ghrelin / endogenous agonist / Class A GPCR / Peptide receptor | ||||||
機能・相同性 | ![]() growth hormone secretagogue receptor activity / regulation of hindgut contraction / ghrelin receptor binding / positive regulation of bone development / positive regulation of gastric mucosal blood circulation / regulation of growth hormone secretion / negative regulation of locomotion / growth hormone-releasing hormone receptor activity / cortisol secretion / positive regulation of small intestinal transit ...growth hormone secretagogue receptor activity / regulation of hindgut contraction / ghrelin receptor binding / positive regulation of bone development / positive regulation of gastric mucosal blood circulation / regulation of growth hormone secretion / negative regulation of locomotion / growth hormone-releasing hormone receptor activity / 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 / negative regulation of locomotion involved in locomotory behavior / regulation of response to food / regulation of gastric motility / guanyl nucleotide binding / regulation of transmission of nerve impulse / gastric acid secretion / positive regulation of corticotropin secretion / response to follicle-stimulating hormone / positive regulation of cortisol secretion / growth hormone secretion / ghrelin secretion / positive regulation of growth rate / positive regulation of eating behavior / negative regulation of norepinephrine secretion / positive regulation of appetite / positive regulation of small intestine smooth muscle contraction / negative regulation of macrophage apoptotic process / adult feeding behavior / positive regulation of growth hormone secretion / negative regulation of appetite / positive regulation of growth hormone receptor signaling pathway / positive regulation of multicellular organism growth / actin polymerization or depolymerization / vesicle docking involved in exocytosis / cellular response to thyroid hormone stimulus / response to growth hormone / positive regulation of synapse assembly / cartilage development / positive regulation of insulin-like growth factor receptor signaling pathway / regulation of neurotransmitter receptor localization to postsynaptic specialization membrane / negative regulation of interleukin-1 beta production / response to food / positive regulation of vascular endothelial cell proliferation / cellular response to insulin-like growth factor stimulus / regulation of postsynapse organization / response to L-glutamate / regulation of synapse assembly / G protein-coupled dopamine receptor signaling pathway / regulation of heart contraction / positive regulation of fatty acid metabolic process / postsynaptic modulation of chemical synaptic transmission / protein tyrosine kinase activator activity / positive regulation of sprouting angiogenesis / response to dexamethasone / dendrite development / negative regulation of endothelial cell proliferation / positive regulation of insulin secretion involved in cellular response to glucose stimulus / peptide hormone binding / negative regulation of interleukin-6 production / negative regulation of tumor necrosis factor production / decidualization / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / Synthesis, secretion, and deacylation of Ghrelin / negative regulation of insulin secretion / G protein-coupled serotonin receptor binding / response to electrical stimulus / synapse assembly / positive regulation of adipose tissue development / excitatory postsynaptic potential / hormone-mediated signaling pathway / negative regulation of angiogenesis / Peptide ligand-binding receptors / insulin-like growth factor receptor signaling pathway / response to hormone / synaptic membrane / locomotory behavior / muscle contraction / G protein-coupled receptor binding / G protein-coupled receptor activity / Schaffer collateral - CA1 synapse / G-protein beta/gamma-subunit complex binding / 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 / G-protein activation / positive regulation of insulin secretion / 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 / ADP signalling through P2Y purinoceptor 12 類似検索 - 分子機能 | ||||||
生物種 | ![]() synthetic construct (人工物) | ||||||
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: 2.8 Å | ||||||
![]() | Qin, J. / Ming, Q. / Ji, S. / Mao, C. / Shen, D. / Zhang, Y. | ||||||
資金援助 | 1件
| ||||||
![]() | ![]() タイトル: Molecular mechanism of agonism and inverse agonism in ghrelin receptor. 著者: Jiao Qin / Ye Cai / Zheng Xu / Qianqian Ming / Su-Yu Ji / Chao Wu / Huibing Zhang / Chunyou Mao / Dan-Dan Shen / Kunio Hirata / Yanbin Ma / Wei Yan / Yan Zhang / Zhenhua Shao / ![]() ![]() 要旨: Much effort has been invested in the investigation of the structural basis of G protein-coupled receptors (GPCRs) activation. Inverse agonists, which can inhibit GPCRs with constitutive activity, are ...Much effort has been invested in the investigation of the structural basis of G protein-coupled receptors (GPCRs) activation. Inverse agonists, which can inhibit GPCRs with constitutive activity, are considered useful therapeutic agents, but the molecular mechanism of such ligands remains insufficiently understood. Here, we report a crystal structure of the ghrelin receptor bound to the inverse agonist PF-05190457 and a cryo-electron microscopy structure of the active ghrelin receptor-Go complex bound to the endogenous agonist ghrelin. Our structures reveal a distinct binding mode of the inverse agonist PF-05190457 in the ghrelin receptor, different from the binding mode of agonists and neutral antagonists. Combining the structural comparisons and cellular function assays, we find that a polar network and a notable hydrophobic cluster are required for receptor activation and constitutive activity. Together, our study provides insights into the detailed mechanism of ghrelin receptor binding to agonists and inverse agonists, and paves the way to design specific ligands targeting ghrelin receptors. | ||||||
履歴 |
|
-
構造の表示
ムービー |
![]() |
---|---|
構造ビューア | 分子: ![]() ![]() |
-
ダウンロードとリンク
-
ダウンロード
PDBx/mmCIF形式 | ![]() | 212.1 KB | 表示 | ![]() |
---|---|---|---|---|
PDB形式 | ![]() | 171.5 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 978.7 KB | 表示 | ![]() |
---|---|---|---|---|
文書・詳細版 | ![]() | 992 KB | 表示 | |
XML形式データ | ![]() | 36.4 KB | 表示 | |
CIF形式データ | ![]() | 55.7 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
-
リンク
-
集合体
登録構造単位 | ![]()
|
---|---|
1 |
|
-
要素
-Guanine nucleotide-binding protein ... , 3種, 3分子 AGB
#1: タンパク質 | 分子量: 26456.100 Da / 分子数: 1 / 変異: G42D,E43N,A227D,G230D,I332A,V335I / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: A0A1W2PS82, UniProt: P09471 |
---|---|
#3: 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) ![]() 発現宿主: ![]() ![]() 参照: UniProt: P59768 |
#5: タンパク質 | 分子量: 37285.734 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: P62873 |
-タンパク質 / 抗体 / タンパク質・ペプチド / 非ポリマー , 4種, 5分子 RSL![](data/chem/img/CLR.gif)
![](data/chem/img/CLR.gif)
#2: タンパク質 | 分子量: 41364.309 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: Q92847 |
---|---|
#4: 抗体 | 分子量: 26610.615 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) synthetic construct (人工物) 発現宿主: ![]() ![]() |
#6: タンパク質・ペプチド | 分子量: 1998.288 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() |
#7: 化合物 |
-詳細
研究の焦点であるリガンドがあるか | Y |
---|
-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
---|---|
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 |
| ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
分子量 | 値: 160.4 MDa / 実験値: YES | ||||||||||||||||||||||||||||||||||||
由来(天然) |
| ||||||||||||||||||||||||||||||||||||
由来(組換発現) |
| ||||||||||||||||||||||||||||||||||||
緩衝液 | pH: 7.5 | ||||||||||||||||||||||||||||||||||||
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 |
---|---|
顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2000 nm / 最小 デフォーカス(公称値): 500 nm |
撮影 | 電子線照射量: 62.24 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
-
解析
ソフトウェア | 名称: PHENIX / バージョン: 1.16_3549: / 分類: 精密化 | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 2.8 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 230306 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
精密化 | 最高解像度: 2.8 Å | ||||||||||||||||||||||||
拘束条件 |
|