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基本情報
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タイトル | Cryo-EM structure of the GTP-bound dopamine receptor 1 and mini-Gs complex without Nb35 | |||||||||
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機能・相同性 | ![]() dopamine neurotransmitter receptor activity, coupled via Gs / dopamine neurotransmitter receptor activity / cerebral cortex GABAergic interneuron migration / Dopamine receptors / operant conditioning / regulation of dopamine uptake involved in synaptic transmission / modification of postsynaptic structure / dopamine binding / heterotrimeric G-protein binding / regulation of dopamine metabolic process ...dopamine neurotransmitter receptor activity, coupled via Gs / dopamine neurotransmitter receptor activity / cerebral cortex GABAergic interneuron migration / Dopamine receptors / operant conditioning / regulation of dopamine uptake involved in synaptic transmission / modification of postsynaptic structure / dopamine binding / heterotrimeric G-protein binding / regulation of dopamine metabolic process / peristalsis / G protein-coupled receptor complex / sensitization / phospholipase C-activating dopamine receptor signaling pathway / grooming behavior / dopamine transport / positive regulation of neuron migration / habituation / astrocyte development / positive regulation of potassium ion transport / striatum development / conditioned taste aversion / dentate gyrus development / maternal behavior / arrestin family protein binding / non-motile cilium / adult walking behavior / long-term synaptic depression / mating behavior / ciliary membrane / G protein-coupled dopamine receptor signaling pathway / temperature homeostasis / dopamine metabolic process / transmission of nerve impulse / glucose import / PKA activation in glucagon signalling / behavioral response to cocaine / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / hair follicle placode formation / neuronal action potential / developmental growth / G-protein alpha-subunit binding / D1 dopamine receptor binding / intracellular transport / GABA-ergic synapse / behavioral fear response / Hedgehog 'off' state / positive regulation of synaptic transmission, glutamatergic / prepulse inhibition / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / synapse assembly / response to amphetamine / adenylate cyclase activator activity / presynaptic modulation of chemical synaptic transmission / positive regulation of release of sequestered calcium ion into cytosol / trans-Golgi network membrane / synaptic transmission, glutamatergic / G protein-coupled receptor activity / long-term synaptic potentiation / regulation of protein phosphorylation / G-protein beta/gamma-subunit complex binding / bone development / visual learning / Olfactory Signaling Pathway / Activation of the phototransduction cascade / vasodilation / 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-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 / cilium / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / memory / cognition / platelet aggregation / 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 / 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 / protein import into nucleus / cellular response to prostaglandin E stimulus 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: 4.16 Å | |||||||||
![]() | Xiao T / Zheng S | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural insights into G protein activation by D1 dopamine receptor. 著者: Xiao Teng / Sijia Chen / Qing Wang / Zhao Chen / Xiaoying Wang / Niu Huang / Sanduo Zheng / ![]() 要旨: G protein-coupled receptors (GPCRs) comprise the largest family of membrane receptors and are the most important drug targets. An agonist-bound GPCR engages heterotrimeric G proteins and triggers the ...G protein-coupled receptors (GPCRs) comprise the largest family of membrane receptors and are the most important drug targets. An agonist-bound GPCR engages heterotrimeric G proteins and triggers the exchange of guanosine diphosphate (GDP) with guanosine triphosphate (GTP) to promote G protein activation. A complete understanding of molecular mechanisms of G protein activation has been hindered by a lack of structural information of GPCR-G protein complex in nucleotide-bound states. Here, we report the cryo-EM structures of the D1 dopamine receptor and mini-G complex in the nucleotide-free and nucleotide-bound states. These structures reveal major conformational changes in Gα such as structural rearrangements of the carboxyl- and amino-terminal α helices that account for the release of GDP and the GTP-dependent dissociation of Gα from Gβγ subunits. As validated by biochemical and cellular signaling studies, our structures shed light into the molecular basis of the entire signaling events of GPCR-mediated G protein activation. | |||||||||
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「今月の分子」の関連する項目 |
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ボクセルのサイズ | X=Y=Z: 1.087 Å | ||||||||||||||||||||
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対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
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試料の構成要素
-全体 : Cryo-EM structure of the GTP-bound dopamine receptor 1 and mini-G...
全体 | 名称: Cryo-EM structure of the GTP-bound dopamine receptor 1 and mini-Gs complex without Nb35 |
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要素 |
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-超分子 #1: Cryo-EM structure of the GTP-bound dopamine receptor 1 and mini-G...
超分子 | 名称: Cryo-EM structure of the GTP-bound dopamine receptor 1 and mini-Gs complex without Nb35 タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#4 |
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由来(天然) | 生物種: ![]() |
組換発現 | 生物種: ![]() |
-分子 #1: Guanine nucleotide-binding protein G(s) subunit alpha isoforms sh...
分子 | 名称: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short,Isoform Gnas-2 of 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: ![]() |
分子量 | 理論値: 28.907684 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: NSKTEDQRNE EKAQREANKK IEKQLQKDKQ VYRATHRLLL LGADNSGKST IVKQMRILHG GSGGSGGTSG IFETKFQVDK VNFHMFDVG GQRDERRKWI QCFNDVTAII FVVDSSDYNR LQEALNLFKS IWNNRWLRTI SVILFLNKQD LLAEKVLAGK S KIEDYFPE ...文字列: NSKTEDQRNE EKAQREANKK IEKQLQKDKQ VYRATHRLLL LGADNSGKST IVKQMRILHG GSGGSGGTSG IFETKFQVDK VNFHMFDVG GQRDERRKWI QCFNDVTAII FVVDSSDYNR LQEALNLFKS IWNNRWLRTI SVILFLNKQD LLAEKVLAGK S KIEDYFPE FARYTTPEDA TPEPGEDPRV TRAKYFIRDE FLRISTASGD GRHYCYPHFT CAVDTENARR IFNDCRDIIQ RM HLRQYEL L |
-分子 #2: D(1A) dopamine receptor
分子 | 名称: D(1A) dopamine receptor / 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: 52.409656 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MKTIIALSYI FCLVFADYKD DDDASIDMRT LNTSAMDGTG LVVERDFSVR ILTACFLSLL ILSTLLGNTL VCAAVIRFRH LRSKVTNFF VISLAVSDLL VAVLVMPWKA VAEIAGFWPF GSFCNIWVAF DIMCSTASIL NLCVISVDRY WAISSPFRYE R KMTPKAAF ...文字列: MKTIIALSYI FCLVFADYKD DDDASIDMRT LNTSAMDGTG LVVERDFSVR ILTACFLSLL ILSTLLGNTL VCAAVIRFRH LRSKVTNFF VISLAVSDLL VAVLVMPWKA VAEIAGFWPF GSFCNIWVAF DIMCSTASIL NLCVISVDRY WAISSPFRYE R KMTPKAAF ILISVAWTLS VLISFIPVQL SWHKAKPTSP SDGNATSLAE TIDNCDSSLS RTYAISSSVI SFYIPVAIMI VT YTRIYRI AQKQIRRIAA LERAAVHAKN CQTTTGNGKP VECSQPESSF KMSFKRETKV LKTLSVIMGV FVCCWLPFFI LNC ILPFCG SGETQPFCID SNTFDVFVWF GWANSSLNPI IYAFNADFRK AFSTLLGCYR LCPATNNAIE TVSINNNGAA MFSS HHEPR GSISKECNLV YLIPHAVGSS EDLKKEEAAG IARPLEKLSP ALSVILDYDT DVSLEKIQPI TQNGQHPT |
-分子 #3: 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: 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: 39.418086 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MHHHHHHLEV LFQGPGSSGS ELDQLRQEAE QLKNQIRDAR KACADATLSQ ITNNIDPVGR IQMRTRRTLR GHLAKIYAMH WGTDSRLLV SASQDGKLII WDSYTTNKVH AIPLRSSWVM TCAYAPSGNY VACGGLDNIC SIYNLKTREG NVRVSRELAG H TGYLSCCR ...文字列: MHHHHHHLEV LFQGPGSSGS ELDQLRQEAE QLKNQIRDAR KACADATLSQ ITNNIDPVGR IQMRTRRTLR GHLAKIYAMH WGTDSRLLV SASQDGKLII WDSYTTNKVH AIPLRSSWVM TCAYAPSGNY VACGGLDNIC SIYNLKTREG NVRVSRELAG H TGYLSCCR FLDDNQIVTS SGDTTCALWD IETGQQTTTF TGHTGDVMSL SLAPDTRLFV SGACDASAKL WDVREGMCRQ TF TGHESDI NAICFFPNGN AFATGSDDAT CRLFDLRADQ ELMTYSHDNI ICGITSVSFS KSGRLLLAGY DDFNCNVWDA LKA DRAGVL AGHDNRVSCL GVTDDGMAVA TGSWDSFLKI WN |
-分子 #4: 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: 4 / 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: 7.845078 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFSAI L |
-分子 #5: GUANOSINE-5'-TRIPHOSPHATE
分子 | 名称: GUANOSINE-5'-TRIPHOSPHATE / タイプ: ligand / ID: 5 / コピー数: 1 / 式: GTP |
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分子量 | 理論値: 523.18 Da |
Chemical component information | ![]() ChemComp-GTP: |
-分子 #6: L-DOPAMINE
分子 | 名称: L-DOPAMINE / タイプ: ligand / ID: 6 / コピー数: 1 / 式: LDP |
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分子量 | 理論値: 153.178 Da |
Chemical component information | ![]() ChemComp-LDP: |
-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
濃度 | 4.0 mg/mL |
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緩衝液 | pH: 7.5 |
グリッド | モデル: Quantifoil R1.2/1.3 / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 281 K / 装置: FEI VITROBOT MARK IV |
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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: 50.0 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 / 倍率(公称値): 64000 |
試料ステージ | ホルダー冷却材: NITROGEN |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |