+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-30505 | |||||||||
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タイトル | Cryo-EM structure of the human growth hormone-releasing hormone receptor-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 intracellular steroid hormone receptor signaling pathway / somatotropin secreting cell development / growth hormone-releasing hormone receptor binding / positive regulation of circadian sleep/wake cycle, REM sleep / growth hormone-releasing hormone receptor activity / growth hormone-releasing hormone activity / growth hormone secretion / adenohypophysis development / positive regulation of growth hormone secretion / regulation of protein metabolic process ...regulation of intracellular steroid hormone receptor signaling pathway / somatotropin secreting cell development / growth hormone-releasing hormone receptor binding / positive regulation of circadian sleep/wake cycle, REM sleep / growth hormone-releasing hormone receptor activity / growth hormone-releasing hormone activity / growth hormone secretion / adenohypophysis development / positive regulation of growth hormone secretion / regulation of protein metabolic process / neuropeptide hormone activity / G-protein activation / Activation of the phototransduction cascade / : / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Ca2+ pathway / positive regulation of multicellular organism growth / Activation of G protein gated Potassium channels / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / multicellular organismal reproductive process / G alpha (z) signalling events / G protein-coupled peptide receptor activity / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / hormone metabolic process / nuclear outer membrane / G alpha (q) signalling events / G alpha (i) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / Adrenaline,noradrenaline inhibits insulin secretion / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Glucagon-type ligand receptors / alkylglycerophosphoethanolamine phosphodiesterase activity / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / positive regulation of insulin-like growth factor receptor signaling pathway / Extra-nuclear estrogen signaling / G alpha (z) signalling events / G alpha (s) signalling events / nuclear inner membrane / G alpha (q) signalling events / response to food / peptide hormone receptor binding / photoreceptor outer segment membrane / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / spectrin binding / Vasopressin regulates renal water homeostasis via Aquaporins / growth factor binding / PKA activation in glucagon signalling / peptide hormone binding / cAMP-mediated signaling / hair follicle placode formation / intracellular transport / photoreceptor outer segment / D1 dopamine receptor binding / developmental growth / Hedgehog 'off' state / positive regulation of cAMP-mediated signaling / adenylate cyclase-activating adrenergic receptor signaling pathway / response to glucocorticoid / cell maturation / cardiac muscle cell apoptotic process / activation of adenylate cyclase activity / photoreceptor inner segment / adenylate cyclase activator activity / 授乳 / trans-Golgi network membrane / 分泌 / G protein-coupled receptor activity / determination of adult lifespan / establishment of localization in cell / G-protein beta/gamma-subunit complex binding / multicellular organism growth / response to insulin / 骨 / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / adenylate cyclase-activating G protein-coupled receptor signaling pathway 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / Rattus norvegicus (ドブネズミ) / Bos taurus (ウシ) / 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: 2.6 Å | |||||||||
データ登録者 | Zhou F / Zhang H / Cong Z / Zhao L / Zhou Q / Mao C / Cheng X / Shen D / Cai X / Ma C ...Zhou F / Zhang H / Cong Z / Zhao L / Zhou Q / Mao C / Cheng X / Shen D / Cai X / Ma C / Wang Y / Dai A / Zhou Y / Sun W / Zhao F / Zhao S / Jiang H / Jiang Y / Yang D / Xu HE / Zhang Y / Wang M | |||||||||
引用 | ジャーナル: Nat Commun / 年: 2020 タイトル: Structural basis for activation of the growth hormone-releasing hormone receptor. 著者: Fulai Zhou / Huibing Zhang / Zhaotong Cong / Li-Hua Zhao / Qingtong Zhou / Chunyou Mao / Xi Cheng / Dan-Dan Shen / Xiaoqing Cai / Cheng Ma / Yuzhe Wang / Antao Dai / Yan Zhou / Wen Sun / ...著者: Fulai Zhou / Huibing Zhang / Zhaotong Cong / Li-Hua Zhao / Qingtong Zhou / Chunyou Mao / Xi Cheng / Dan-Dan Shen / Xiaoqing Cai / Cheng Ma / Yuzhe Wang / Antao Dai / Yan Zhou / Wen Sun / Fenghui Zhao / Suwen Zhao / Hualiang Jiang / Yi Jiang / Dehua Yang / H Eric Xu / Yan Zhang / Ming-Wei Wang / 要旨: Growth hormone-releasing hormone (GHRH) regulates the secretion of growth hormone that virtually controls metabolism and growth of every tissue through its binding to the cognate receptor (GHRHR). ...Growth hormone-releasing hormone (GHRH) regulates the secretion of growth hormone that virtually controls metabolism and growth of every tissue through its binding to the cognate receptor (GHRHR). Malfunction in GHRHR signaling is associated with abnormal growth, making GHRHR an attractive therapeutic target against dwarfism (e.g., isolated growth hormone deficiency, IGHD), gigantism, lipodystrophy and certain cancers. Here, we report the cryo-electron microscopy (cryo-EM) structure of the human GHRHR bound to its endogenous ligand and the stimulatory G protein at 2.6 Å. This high-resolution structure reveals a characteristic hormone recognition pattern of GHRH by GHRHR, where the α-helical GHRH forms an extensive and continuous network of interactions involving all the extracellular loops (ECLs), all the transmembrane (TM) helices except TM4, and the extracellular domain (ECD) of GHRHR, especially the N-terminus of GHRH that engages a broad set of specific interactions with the receptor. Mutagenesis and molecular dynamics (MD) simulations uncover detailed mechanisms by which IGHD-causing mutations lead to the impairment of GHRHR function. Our findings provide insights into the molecular basis of peptide recognition and receptor activation, thereby facilitating the development of structure-based drug discovery and precision medicine. | |||||||||
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_30505.map.gz | 40 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-30505-v30.xml emd-30505.xml | 21.2 KB 21.2 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_30505.png | 48.6 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-30505 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-30505 | 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_30505.map.gz / 形式: CCP4 / 大きさ: 42.9 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: 1.014 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
-試料の構成要素
+全体 : Growth hormone-releasing hormone receptor - Gs protein complex
+超分子 #1: Growth hormone-releasing hormone receptor - Gs protein complex
+超分子 #2: hormone receptor, G(s) subunit alpha isoforms
+超分子 #3: hormone
+超分子 #4: G(s) subunit beta-1
+超分子 #5: G(s) subunit gamma-2
+超分子 #6: Nanobody35
+分子 #1: Growth hormone-releasing hormone receptor,growth hormone-releasin...
+分子 #2: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
+分子 #3: Somatoliberin
+分子 #4: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+分子 #5: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+分子 #6: Nanobody35
+分子 #7: PALMITIC ACID
+分子 #8: CHOLESTEROL
+分子 #9: 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
緩衝液 | pH: 7.5 |
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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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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 FIELDBright-field microscopy |
撮影 | フィルム・検出器のモデル: GATAN K2 QUANTUM (4k x 4k) 検出モード: COUNTING / 平均電子線量: 62.0 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: EMDB MAP EMDB ID: |
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初期 角度割当 | タイプ: RANDOM ASSIGNMENT |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 2.6 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 307018 |