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基本情報
登録情報 | ![]() | |||||||||
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タイトル | Cryo-EM structure of histamine H3 receptor in complex with immethridine and miniGo | |||||||||
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![]() | GPCR / SIGNALING PROTEIN | |||||||||
機能・相同性 | ![]() Histamine receptors / histamine receptor activity / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / neurotransmitter receptor activity / mu-type opioid receptor binding / neurotransmitter secretion / corticotropin-releasing hormone receptor 1 binding / vesicle docking involved in exocytosis / G protein-coupled dopamine receptor signaling pathway / regulation of heart contraction ...Histamine receptors / histamine receptor activity / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / neurotransmitter receptor activity / mu-type opioid receptor binding / neurotransmitter secretion / corticotropin-releasing hormone receptor 1 binding / vesicle docking involved in exocytosis / G protein-coupled dopamine receptor signaling pathway / regulation of heart contraction / parallel fiber to Purkinje cell synapse / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / postsynaptic modulation of chemical synaptic transmission / negative regulation of insulin secretion / G protein-coupled serotonin receptor binding / adenylate cyclase regulator activity / adenylate cyclase-inhibiting serotonin receptor signaling pathway / muscle contraction / GABA-ergic synapse / locomotory behavior / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / adenylate cyclase-activating dopamine receptor signaling pathway / GPER1 signaling / Inactivation, recovery and regulation of the phototransduction cascade / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / sensory perception of taste / extracellular vesicle / signaling receptor complex adaptor activity / presynapse / Thrombin signalling through proteinase activated receptors (PARs) / presynaptic membrane / G protein activity / cell body / GTPase binding / Ca2+ pathway / retina development in camera-type eye / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / fibroblast proliferation / G alpha (i) signalling events / 加水分解酵素; 酸無水物に作用; GTPに作用・細胞または細胞小器官の運動に関与 / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / chemical synaptic transmission / G alpha (q) signalling events / postsynaptic membrane / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell population proliferation / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / dendrite / protein-containing complex binding / GTP binding / glutamatergic synapse / signal transduction / extracellular exosome / metal ion binding / membrane / plasma membrane / cytosol / cytoplasm 類似検索 - 分子機能 | |||||||||
生物種 | ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.77 Å | |||||||||
![]() | Zhang X / Liu G / Li X / Gong W | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural basis of ligand recognition and activation of the histamine receptor family. 著者: Xuan Zhang / Guibing Liu / Ya-Ni Zhong / Ru Zhang / Chuan-Cheng Yang / Canyang Niu / Xuanyu Pu / Jingjing Sun / Tianyao Zhang / Lejin Yang / Chao Zhang / Xiu Li / Xinyuan Shen / Peng Xiao / ...著者: Xuan Zhang / Guibing Liu / Ya-Ni Zhong / Ru Zhang / Chuan-Cheng Yang / Canyang Niu / Xuanyu Pu / Jingjing Sun / Tianyao Zhang / Lejin Yang / Chao Zhang / Xiu Li / Xinyuan Shen / Peng Xiao / Jin-Peng Sun / Weimin Gong / ![]() ![]() 要旨: Histamine is a biogenic amine that is critical in various physiological and pathophysiological processes, including but not limited to allergic reactions, wakefulness, gastric acid secretion and ...Histamine is a biogenic amine that is critical in various physiological and pathophysiological processes, including but not limited to allergic reactions, wakefulness, gastric acid secretion and neurotransmission. Here, we determine 9 cryo-electron microscopy (cryo-EM) structures of the 4 histamine receptors in complex with four different G protein subtypes, with endogenous or synthetic agonists bound. Inside the ligand pocket, we identify key motifs for the recognition of histamine, the distinct binding orientations of histamine and three subpockets that facilitate the design of specific ligands. In addition, we also identify key residues responsible for the selectivity of immethridine. Moreover, we reveal distinct structural features as determinants of Gq vs. Gs or Gs vs. Gi coupling differences among the histamine receptors. Our study provides a structural framework for understanding the ligand recognition and G protein coupling of all 4 histamine receptors, which may facilitate the rational design of ligands targeting these receptors. | |||||||||
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 | ![]() | 18.2 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 20.3 KB 20.3 KB | 表示 表示 | ![]() |
画像 | ![]() | 77.1 KB | ||
Filedesc metadata | ![]() | 6.8 KB | ||
その他 | ![]() ![]() | 20.6 MB 20.6 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 8yn7MC ![]() 8yn2C ![]() 8yn3C ![]() 8yn4C ![]() 8yn5C ![]() 8yn6C ![]() 8yn8C ![]() 8yn9C ![]() 8ynaC 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 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||||||||||||||||||
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投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.07 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: #1
ファイル | emd_39417_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: #2
ファイル | emd_39417_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 |
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試料の構成要素
-全体 : Immethridine-H3R-miniGo-scFv16 complex
全体 | 名称: Immethridine-H3R-miniGo-scFv16 complex |
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要素 |
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-超分子 #1: Immethridine-H3R-miniGo-scFv16 complex
超分子 | 名称: Immethridine-H3R-miniGo-scFv16 complex / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#5 |
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由来(天然) | 生物種: ![]() |
-分子 #1: Engineered guanine nucleotide-binding protein G(o) subunit alpha,...
分子 | 名称: Engineered guanine nucleotide-binding protein G(o) subunit alpha,Guanine nucleotide-binding protein G(o) subunit alpha タイプ: protein_or_peptide / ID: 1 詳細: Residues 232-241 of the wild-type protein were truncated in this engineered protein. コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: synthetic construct (人工物) |
分子量 | 理論値: 25.286922 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MTLSAEERAA LERSKAIEKN LKEDGISAAK DVKLLLLGAD NSGKSTIVKQ MKIIHGGSGG SGGTTGIVET HFTFKNLHFR LFDVGGQRS ERKKWIHCFE DVTAIIFCVD LSDYNRMHES LMLFDSICNN KFFIDTSIIL FLNKKDLFGE KIKKSPLTIC F PEYTGPNT ...文字列: MTLSAEERAA LERSKAIEKN LKEDGISAAK DVKLLLLGAD NSGKSTIVKQ MKIIHGGSGG SGGTTGIVET HFTFKNLHFR LFDVGGQRS ERKKWIHCFE DVTAIIFCVD LSDYNRMHES LMLFDSICNN KFFIDTSIIL FLNKKDLFGE KIKKSPLTIC F PEYTGPNT YEDAAAYIQA QFESKNRSPN KEIYCHMTCA TDTNNAQVIF DAVTDIIIAN NLRGCGLY UniProtKB: Guanine nucleotide-binding protein G(o) subunit alpha |
-分子 #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
分子 | 名称: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 40.845559 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MHHHHHHGSS GSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKL IIWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC R FLDDNQIV ...文字列: MHHHHHHGSS GSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKL IIWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC R FLDDNQIV TSSGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KLWDVREGMC RQTFTGHESD IN AICFFPN GNAFATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYDDFNCNVW DALKADRAGV LAG HDNRVS CLGVTDDGMA VATGSWDSFL KIWNGSSGGG GSGGGGSSGV SGWRLFKKIS UniProtKB: 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 | 名称: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 7.861143 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-分子 #4: Antibody fragment scFv16
分子 | 名称: Antibody fragment scFv16 / タイプ: protein_or_peptide / ID: 4 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: synthetic construct (人工物) |
分子量 | 理論値: 27.314422 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: VQLVESGGGL VQPGGSRKLS CSASGFAFSS FGMHWVRQAP EKGLEWVAYI SSGSGTIYYA DTVKGRFTIS RDDPKNTLFL QMTSLRSED TAMYYCVRSI YYYGSSPFDF WGQGTTLTVS AGGGGSGGGG SGGGGSADIV MTQATSSVPV TPGESVSISC R SSKSLLHS ...文字列: VQLVESGGGL VQPGGSRKLS CSASGFAFSS FGMHWVRQAP EKGLEWVAYI SSGSGTIYYA DTVKGRFTIS RDDPKNTLFL QMTSLRSED TAMYYCVRSI YYYGSSPFDF WGQGTTLTVS AGGGGSGGGG SGGGGSADIV MTQATSSVPV TPGESVSISC R SSKSLLHS NGNTYLYWFL QRPGQSPQLL IYRMSNLASG VPDRFSGSGS GTAFTLTISR LEAEDVGVYY CMQHLEYPLT FG AGTKLEL LEENLYFQ |
-分子 #5: Histamine H3 receptor
分子 | 名称: Histamine H3 receptor / タイプ: protein_or_peptide / ID: 5 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 72.568703 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: DYKDDDDHHH HHHHHGQPGN GSAFLLAPNG SHAPDHNVTQ QRDEENLYFQ GVDMERAPPD GPLNASGALA GEAAAAGGAR GFSAAWTAV LAALMALLIV ATVLGNALVM LAFVADSSLR TQNNFFLLNL AISDFLVGAF CIPLYVPYVL TGRWTFGRGL C KLWLVVDY ...文字列: DYKDDDDHHH HHHHHGQPGN GSAFLLAPNG SHAPDHNVTQ QRDEENLYFQ GVDMERAPPD GPLNASGALA GEAAAAGGAR GFSAAWTAV LAALMALLIV ATVLGNALVM LAFVADSSLR TQNNFFLLNL AISDFLVGAF CIPLYVPYVL TGRWTFGRGL C KLWLVVDY LLCTSSAFNI VLISYDRFLS VTRAVSYRAQ QGDTRRAVRK MLLVWVLAFL LYGPAILSWE YLSGGSSIPE GH CYAEFFY NWYFLITAST LEFFTPFLSV TFFNLSIYLN IQRRTRLRLD GAREAAGPEP PPEAQPSPPP PPGCWGCWQK GHG EAMPLH RYGVGEAAVG AEAGEATLGG GGGGGSVASP TSSSGSSSRG TERPRSLKRG SKPSASSASL EKRMKMVSQS FTQR FRLSR DRKVAKSLAV IVSIFGLCWA PYTLLMIIRA ACHGHCVPDY WYETSFWLLW ANSAVNPVLY PLCHHSFRRA FTKLL CPQK LKIQPHSSLE HCWKAAAVFT LEDFVGDWEQ TAAYNLDQVL EQGGVSSLLQ NLAVSVTPIQ RIVRSGENAL KIDIHV IIP YEGLSADQMA QIEEVFKVVY PVDDHHFKVI LPYGTLVIDG VTPNMLNYFG RPYEGIAVFD GKKITVTGTL WNGNKII DE RLITPDGSML FRVTINS UniProtKB: Histamine H3 receptor |
-分子 #6: 4-(1H-imidazol-4-ylmethyl)pyridine
分子 | 名称: 4-(1H-imidazol-4-ylmethyl)pyridine / タイプ: ligand / ID: 6 / コピー数: 1 / 式: A1LY2 |
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分子量 | 理論値: 159.188 Da |
-分子 #7: CHOLESTEROL
分子 | 名称: CHOLESTEROL / タイプ: ligand / ID: 7 / コピー数: 5 / 式: CLR |
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分子量 | 理論値: 386.654 Da |
Chemical component information | ![]() ChemComp-CLR: |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
緩衝液 | pH: 7.5 |
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凍結 | 凍結剤: ETHANE |
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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 BIOQUANTUM (6k x 4k) 平均電子線量: 55.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
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): 2.2 µm / 最小 デフォーカス(公称値): 1.2 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
初期モデル | モデルのタイプ: INSILICO MODEL |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 2.77 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 160325 |
初期 角度割当 | タイプ: PROJECTION MATCHING |
最終 角度割当 | タイプ: PROJECTION MATCHING |