+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-36951 | |||||||||
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タイトル | Cannabinoid Receptor 1 bound to Fenofibrate coupling MiniGsq and Nb35 Complex | |||||||||
マップデータ | ||||||||||
試料 |
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キーワード | GPCR (Gタンパク質共役受容体) / MEMBRANE PROTEIN (膜タンパク質) | |||||||||
機能・相同性 | 機能・相同性情報 cannabinoid signaling pathway / regulation of penile erection / retrograde trans-synaptic signaling by endocannabinoid / cannabinoid receptor activity / negative regulation of mast cell activation / trans-synaptic signaling by endocannabinoid, modulating synaptic transmission / negative regulation of fatty acid beta-oxidation / negative regulation of dopamine secretion / positive regulation of acute inflammatory response to antigenic stimulus / regulation of feeding behavior ...cannabinoid signaling pathway / regulation of penile erection / retrograde trans-synaptic signaling by endocannabinoid / cannabinoid receptor activity / negative regulation of mast cell activation / trans-synaptic signaling by endocannabinoid, modulating synaptic transmission / negative regulation of fatty acid beta-oxidation / negative regulation of dopamine secretion / positive regulation of acute inflammatory response to antigenic stimulus / regulation of feeding behavior / negative regulation of serotonin secretion / regulation of presynaptic cytosolic calcium ion concentration / negative regulation of action potential / Class A/1 (Rhodopsin-like receptors) / positive regulation of blood pressure / positive regulation of fever generation / regulation of metabolic process / axonal fasciculation / regulation of synaptic transmission, GABAergic / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / PKA activation in glucagon signalling / regulation of insulin secretion / hair follicle placode formation / developmental growth / D1 dopamine receptor binding / maternal process involved in female pregnancy / GABA-ergic synapse / intracellular transport / Hedgehog 'off' state / positive regulation of cAMP-mediated signaling / adenylate cyclase-activating adrenergic receptor signaling pathway / regulation of synaptic transmission, glutamatergic / activation of adenylate cyclase activity / adenylate cyclase activator activity / negative regulation of blood pressure / response to nutrient / trans-Golgi network membrane / response to cocaine / response to nicotine / G protein-coupled receptor activity / Olfactory Signaling Pathway / G-protein beta/gamma-subunit complex binding / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / 骨 / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / 記憶 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / 血小板 / 認識 / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / positive regulation of GTPase activity / positive regulation of neuron projection development / 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 / 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 / sensory perception of smell / Thrombin signalling through proteinase activated receptors (PARs) / マイクロフィラメント / glucose homeostasis / retina development in camera-type eye / presynaptic membrane / GTPase binding / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cold-induced thermogenesis / G alpha (i) signalling events / 成長円錐 / fibroblast proliferation / G alpha (s) signalling events 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.88 Å | |||||||||
データ登録者 | Tang WQ / Wang TX / Li FH / Wang JY | |||||||||
資金援助 | 中国, 1件
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引用 | ジャーナル: Adv Sci (Weinh) / 年: 2024 タイトル: Fenofibrate Recognition and G Protein Coupling Mechanisms of the Human Cannabinoid Receptor CB1. 著者: Tianxin Wang / Wenqin Tang / Ziyi Zhao / Ran Zhao / Zhenyu Lv / Xuzhen Guo / Quanchang Gu / Boxiang Liu / Haoyu Lv / Jiayan Chen / Kaiquan Zhang / Fahui Li / Jiangyun Wang / 要旨: The G-protein-coupled human cannabinoid receptor 1 (CB1) is a promising therapeutic target for pain management, inflammation, obesity, and substance abuse disorders. The structures of CB1-G complexes ...The G-protein-coupled human cannabinoid receptor 1 (CB1) is a promising therapeutic target for pain management, inflammation, obesity, and substance abuse disorders. The structures of CB1-G complexes in synthetic agonist-bound forms have been resolved to date. However, the commercial drug recognition and G coupling mechanisms of CB1 remain elusive. Herein, the cryo-electron microscopy (cryo-EM) structure of CB1-G complex, in fenofibrate-bound form, at near-atomic resolution, is reported. The structure elucidates the delicate mechanisms of the precise fenofibrate recognition and G protein coupling by CB1 and will facilitate future drug discovery and design. | |||||||||
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_36951.map.gz | 114.4 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-36951-v30.xml emd-36951.xml | 16 KB 16 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_36951.png | 64.3 KB | ||
Filedesc metadata | emd-36951.cif.gz | 6.5 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-36951 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36951 | HTTPS FTP |
-関連構造データ
関連構造データ | 8k8jMC C: 同じ文献を引用 (文献) M: このマップから作成された原子モデル |
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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_36951.map.gz / 形式: CCP4 / 大きさ: 125 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: 0.832 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
-試料の構成要素
-全体 : Cannabinoid Receptor 1-G protein complex
全体 | 名称: Cannabinoid Receptor 1-G protein complex |
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要素 |
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-超分子 #1: Cannabinoid Receptor 1-G protein complex
超分子 | 名称: Cannabinoid Receptor 1-G protein complex / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #5, #1-#4 |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
分子 | 名称: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 30.652561 KDa |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: MGHHHHHHEN LYFQGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGADN SGKSTIVKQM RILHGGSGGS GGTSGIFET KFQVDKVNFH MFDVGGQRDE RRKWIQCFND VTAIIFVVDS SDYNRLQEAL NLFKSIWNNR WLRTISVILF L NKQDLLAE ...文字列: MGHHHHHHEN LYFQGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGADN SGKSTIVKQM RILHGGSGGS GGTSGIFET KFQVDKVNFH MFDVGGQRDE RRKWIQCFND VTAIIFVVDS SDYNRLQEAL NLFKSIWNNR WLRTISVILF L NKQDLLAE KVLAGKSKIE DYFPEFARYT TPEDATPEPG EDPRVTRAKY FIRDEFLRIS TASGDGRHYC YPHFTCAVDT EN ARRIFND CKDIILQMNL REYNLV UniProtKB: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short |
-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: Homo sapiens (ヒト) |
分子量 | 理論値: 37.41693 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL ...文字列: MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KLWDVREGMC RQTFTGHESD INAICFFPNG NA FATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYDDFNCNVW DALKADRAGV LAGHDNRVSC LGV TDDGMA VATGSWDSFL KIWN 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: Homo sapiens (ヒト) |
分子量 | 理論値: 10.49796 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MHHHHHHGGG SDSLEFIASK LAGGGSMASN NTASIAQARK LVEQLKMEAN IDRIKVSKAA ADLMAYCEAH AKEDPLLTPV PASENPFRE KKFFSAIL UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-分子 #4: Nanobody 35
分子 | 名称: Nanobody 35 / 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: Homo sapiens (ヒト) |
分子量 | 理論値: 15.271938 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MQVQLQESGG GLVQPGGSLR LSCAASGFTF SNYKMNWVRQ APGKGLEWVS DISQSGASIS YTGSVKGRFT ISRDNAKNTL YLQMNSLKP EDTAVYYCAR CPAPFTRDCF DVTSTTYAYR GQGTQVTVSS HHHHHHEPEA |
-分子 #5: Soluble cytochrome b562,Cannabinoid receptor 1
分子 | 名称: Soluble cytochrome b562,Cannabinoid receptor 1 / 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: Homo sapiens (ヒト) |
分子量 | 理論値: 59.685355 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MKTIIALSYI FCLVFADYKD DDDAKLQTMH HHHHHHHHHE NLYFQGGGRA DLEDNWETLN DNLKVIEKAD NAAQVKDALT KMRAAALDA QKATPPKLED KSPDSPEMKD FRHGFDILVG QIDDALKLAN EGKVKEAQAA AEQLKTTRNA YIQKYLLEVL F QGPVPADQ ...文字列: MKTIIALSYI FCLVFADYKD DDDAKLQTMH HHHHHHHHHE NLYFQGGGRA DLEDNWETLN DNLKVIEKAD NAAQVKDALT KMRAAALDA QKATPPKLED KSPDSPEMKD FRHGFDILVG QIDDALKLAN EGKVKEAQAA AEQLKTTRNA YIQKYLLEVL F QGPVPADQ VNITEFYNKS LSSFKENEEN IQCGENFMDI ECFMVLNPSQ QLAIAVLSLT LGTFTVLENL LVLCVILHSR SL RCRPSYH FIGSLAVADL LGSVIFVYSF IDFHVFHRKD SRNVFLFKLG GVTASFTASV GSLFLIAIDR YISIHRPLAY KRI VTRPKA VVAFCLMWTI AIVIAVLPLL GWNCEKLQSV CSDIFPHIDK TYLMFWIGVV SVLLLFIVYA YMYILWKAHS HAVR MIQRG TQKSIIIHTS EDGKVQVTRP DQARMDIELA KTLVLILVVL IICWGPLLAI MVYDVFGKMN KLIKTVFAFC SMLCL LNST VNPIIYALRS KDLRHAFRSM FPSCEGTAQP LDNSHHHHHH H UniProtKB: Soluble cytochrome b562, Cannabinoid receptor 1 |
-分子 #6: propan-2-yl 2-[4-(4-chlorophenyl)carbonylphenoxy]-2-methyl-propanoate
分子 | 名称: propan-2-yl 2-[4-(4-chlorophenyl)carbonylphenoxy]-2-methyl-propanoate タイプ: ligand / ID: 6 / コピー数: 1 / 式: J3O |
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分子量 | 理論値: 360.831 Da |
-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 / 最大 デフォーカス(公称値): 2.0 µm / 最小 デフォーカス(公称値): 0.8 µm |
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 |
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 PDBモデル - PDB 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: 2.88 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 352452 |