+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-34371 | |||||||||
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タイトル | Cryo-EM structure of ACTH-bound melanocortin-2 receptor in complex with MRAP1 and Gs protein | |||||||||
マップデータ | ||||||||||
試料 |
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機能・相同性 | 機能・相同性情報 corticotropin receptor activity / corticotropin hormone receptor binding / type 5 melanocortin receptor binding / Defective ACTH causes obesity and POMCD / type 1 melanocortin receptor binding / type 3 melanocortin receptor binding / type 4 melanocortin receptor binding / melanocortin receptor activity / signaling receptor regulator activity / sensory perception of chemical stimulus ...corticotropin receptor activity / corticotropin hormone receptor binding / type 5 melanocortin receptor binding / Defective ACTH causes obesity and POMCD / type 1 melanocortin receptor binding / type 3 melanocortin receptor binding / type 4 melanocortin receptor binding / melanocortin receptor activity / signaling receptor regulator activity / sensory perception of chemical stimulus / negative regulation of adenylate cyclase activity / negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / regulation of metabolic process / GTP metabolic process / negative regulation of protein localization to plasma membrane / G protein-coupled dopamine receptor signaling pathway / positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / PKA activation in glucagon signalling / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / positive regulation of macroautophagy / mu-type opioid receptor binding / developmental growth / corticotropin-releasing hormone receptor 1 binding / D1 dopamine receptor binding / Adenylate cyclase inhibitory pathway / Hedgehog 'off' state / beta-2 adrenergic receptor binding / adenylate cyclase activator activity / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Peptide ligand-binding receptors / protein localization to plasma membrane / G protein-coupled receptor binding / G protein-coupled receptor activity / electron transport chain / 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 activation / hormone activity / 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 / 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 / platelet aggregation / 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 / GDP binding / G-protein beta-subunit binding / 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) / GTPase binding / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / positive regulation of cold-induced thermogenesis / midbody / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / periplasmic space / electron transfer activity / cell cycle / iron ion binding / G protein-coupled receptor signaling pathway 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / 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: 3.3 Å | |||||||||
データ登録者 | Luo P / Feng WB / Ma SS / Dai AT / Yuan QN / Wu K / Yang DH / Wang MW / Xu HE / Jiang Y | |||||||||
資金援助 | 中国, 1件
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引用 | ジャーナル: Cell Res / 年: 2023 タイトル: Structural basis of signaling regulation of the human melanocortin-2 receptor by MRAP1. 著者: Ping Luo / Wenbo Feng / Shanshan Ma / Antao Dai / Kai Wu / Xianyue Chen / Qingning Yuan / Xiaoqing Cai / Dehua Yang / Ming-Wei Wang / H Eric Xu / Yi Jiang / 要旨: G protein-coupled receptors (GPCRs) are regulated by various downstream proteins, of which the melanocortin receptor accessory protein 1 (MRAP1) is closely involved in the regulation of melanocortin ...G protein-coupled receptors (GPCRs) are regulated by various downstream proteins, of which the melanocortin receptor accessory protein 1 (MRAP1) is closely involved in the regulation of melanocortin receptor 2 (MC2R). Assisted by MRAP1, MC2R responds to adrenocorticotropic hormone (ACTH) and stimulates glucocorticoid biogenesis and cortisol secretion. MC2R activation plays an essential role in the hypothalamic-pituitary-adrenal (HPA) axis that regulates stress response, while its dysfunction causes glucocorticoid insufficiency- or cortisol excess-associated disorders. Here, we present a cryo-electron microscopy (cryo-EM) structure of the ACTH-bound MC2R-G-MRAP1 complex. Our structure, together with mutagenesis analysis, reveals a unique sharp kink at the extracellular region of MRAP1 and the 'seat-belt' effect of MRAP1 on stabilizing ACTH binding and MC2R activation. Mechanisms of ACTH recognition by MC2R and receptor activation are also demonstrated. These findings deepen our understanding of GPCR regulation by accessory proteins and provide valuable insights into the ab initio design of therapeutic agents targeting MC2R. | |||||||||
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_34371.map.gz | 47 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-34371-v30.xml emd-34371.xml | 23.5 KB 23.5 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_34371.png | 40.7 KB | ||
その他 | emd_34371_half_map_1.map.gz emd_34371_half_map_2.map.gz | 40.8 MB 40.8 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-34371 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-34371 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_34371_validation.pdf.gz | 603.2 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_34371_full_validation.pdf.gz | 602.8 KB | 表示 | |
XML形式データ | emd_34371_validation.xml.gz | 11.4 KB | 表示 | |
CIF形式データ | emd_34371_validation.cif.gz | 13.1 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-34371 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-34371 | HTTPS FTP |
-関連構造データ
関連構造データ | 8gy7MC 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_34371.map.gz / 形式: CCP4 / 大きさ: 52.7 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: 1.04 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
-ハーフマップ: #2
ファイル | emd_34371_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_34371_half_map_2.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 : ACTH-bound melanocortin-2 receptor in complex with MRAP1 and Gs p...
+超分子 #1: ACTH-bound melanocortin-2 receptor in complex with MRAP1 and Gs p...
+超分子 #2: Guanine nucleotide-binding protein G(i) subunit alpha-1
+超分子 #3: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+超分子 #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+超分子 #5: ACTH
+超分子 #6: MRAP1
+超分子 #7: melanocortin-2 receptor
+分子 #1: Guanine nucleotide-binding protein G(i) subunit alpha-3,Guanine n...
+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: Corticotropin
+分子 #5: Melanocortin-2 receptor accessory protein
+分子 #6: Soluble cytochrome b562,Adrenocorticotropic hormone receptor,mela...
+分子 #7: CALCIUM ION
-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: 7.2 |
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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: 60.0 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: FLOOD BEAM / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 3.0 µm / 最小 デフォーカス(公称値): 1.0 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 59170 |
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初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |