+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-11927 | |||||||||
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タイトル | Melanocortin receptor 4 (MC4R) Gs protein complex | |||||||||
マップデータ | ||||||||||
試料 |
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機能・相同性 | 機能・相同性情報 regulation of eating behavior / melanocyte-stimulating hormone receptor activity / response to melanocyte-stimulating hormone / melanocortin receptor activity / regulation of grooming behavior / energy reserve metabolic process / neuropeptide binding / regulation of metabolic process / feeding behavior / insulin secretion ...regulation of eating behavior / melanocyte-stimulating hormone receptor activity / response to melanocyte-stimulating hormone / melanocortin receptor activity / regulation of grooming behavior / energy reserve metabolic process / neuropeptide binding / regulation of metabolic process / feeding behavior / insulin secretion / diet induced thermogenesis / negative regulation of feeding behavior / PKA activation in glucagon signalling / peptide hormone binding / hair follicle placode formation / intracellular transport / D1 dopamine receptor binding / developmental growth / positive regulation of bone resorption / Hedgehog 'off' state / positive regulation of cAMP-mediated signaling / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / adenylate cyclase activator activity / Peptide ligand-binding receptors / trans-Golgi network membrane / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / response to insulin / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / 骨 / 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / 血小板 / Glucagon-type ligand receptors / 認識 / Vasopressin regulates renal water homeostasis via Aquaporins / positive regulation of GTPase activity / G alpha (z) signalling events / cellular response to catecholamine stimulus / 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 / sensory perception of taste / GPER1 signaling / G-protein beta-subunit binding / heterotrimeric G-protein complex / Inactivation, recovery and regulation of the phototransduction cascade / extracellular vesicle / G alpha (12/13) signalling events / signaling receptor complex adaptor activity / sensory perception of smell / 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 / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / シナプス / ubiquitin protein ligase binding / protein-containing complex binding / GTP binding / シグナル伝達 / extracellular exosome / 生体膜 / metal ion binding / 細胞膜 / 細胞質基質 / 細胞質 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / Mus musculus (ハツカネズミ) / synthetic construct (人工物) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.97 Å | |||||||||
データ登録者 | Degtjarik O / Israeli H / Prabahar V / Shalev-Benami M | |||||||||
引用 | ジャーナル: Science / 年: 2021 タイトル: Structure reveals the activation mechanism of the MC4 receptor to initiate satiation signaling. 著者: Hadar Israeli / Oksana Degtjarik / Fabrizio Fierro / Vidicha Chunilal / Amandeep Kaur Gill / Nicolas J Roth / Joaquin Botta / Vadivel Prabahar / Yoav Peleg / Li F Chan / Danny Ben-Zvi / Peter ...著者: Hadar Israeli / Oksana Degtjarik / Fabrizio Fierro / Vidicha Chunilal / Amandeep Kaur Gill / Nicolas J Roth / Joaquin Botta / Vadivel Prabahar / Yoav Peleg / Li F Chan / Danny Ben-Zvi / Peter J McCormick / Masha Y Niv / Moran Shalev-Benami / 要旨: Obesity is a global epidemic that causes morbidity and impaired quality of life. The melanocortin receptor 4 (MC4R) is at the crux of appetite, energy homeostasis, and body-weight control in the ...Obesity is a global epidemic that causes morbidity and impaired quality of life. The melanocortin receptor 4 (MC4R) is at the crux of appetite, energy homeostasis, and body-weight control in the central nervous system and is a prime target for anti-obesity drugs. Here, we present the cryo-electron microscopy (cryo-EM) structure of the human MC4R-G signaling complex bound to the agonist setmelanotide, a cyclic peptide recently approved for the treatment of obesity. The work reveals the mechanism of MC4R activation, highlighting a molecular switch that initiates satiation signaling. In addition, our findings indicate that calcium (Ca) is required for agonist, but not antagonist, efficacy. These results fill a gap in the understanding of MC4R activation and could guide the design of future weight-management drugs. | |||||||||
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_11927.map.gz | 78.3 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-11927-v30.xml emd-11927.xml | 20.1 KB 20.1 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_11927.png | 173.8 KB | ||
その他 | emd_11927_additional_1.map.gz | 65.1 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-11927 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-11927 | 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_11927.map.gz / 形式: CCP4 / 大きさ: 83.7 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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
-追加マップ: #1
ファイル | emd_11927_additional_1.map | ||||||||||||
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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 : Melanocortine 4 (MC4R) - GalphaS protein comlex
+超分子 #1: Melanocortine 4 (MC4R) - GalphaS protein comlex
+超分子 #2: Melanocortine 4 (MC4R) - GalphaS protein comlex
+超分子 #3: scFv16
+超分子 #4: AMINOSERINE
+分子 #1: Melanocortin receptor 4
+分子 #2: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
+分子 #3: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+分子 #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+分子 #5: scFv16
+分子 #6: AMINOSERINE
+分子 #7: CALCIUM ION
+分子 #8: water
-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 | 14 mg/mL |
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緩衝液 | pH: 7.5 |
グリッド | モデル: Quantifoil R1.2/1.3 / 材質: GOLD / メッシュ: 200 / 前処理 - タイプ: GLOW DISCHARGE |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 295 K / 装置: FEI VITROBOT MARK IV |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | C2レンズ絞り径: 100.0 µm / 照射モード: OTHER / 撮影モード: BRIGHT FIELDBright-field microscopy |
撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 平均電子線量: 45.5 e/Å2 |
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 / 詳細: 6W25, 6N4B |
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初期 角度割当 | タイプ: OTHER |
最終 角度割当 | タイプ: OTHER |
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 2.97 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 366496 |