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基本情報
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タイトル | Cryo-EM structure of the GDP-bound dopamine receptor 1 and mini-Gs complex with Nb35 | |||||||||
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機能・相同性 | ![]() dopamine neurotransmitter receptor activity / cerebral cortex GABAergic interneuron migration / Dopamine receptors / operant conditioning / dopamine neurotransmitter receptor activity, coupled via Gs / dopamine binding / regulation of dopamine uptake involved in synaptic transmission / modification of postsynaptic structure / heterotrimeric G-protein binding / regulation of dopamine metabolic process ...dopamine neurotransmitter receptor activity / cerebral cortex GABAergic interneuron migration / Dopamine receptors / operant conditioning / dopamine neurotransmitter receptor activity, coupled via Gs / dopamine binding / regulation of dopamine uptake involved in synaptic transmission / modification of postsynaptic structure / heterotrimeric G-protein binding / regulation of dopamine metabolic process / sensitization / peristalsis / G protein-coupled receptor complex / phospholipase C-activating dopamine receptor signaling pathway / dopamine transport / grooming behavior / positive regulation of neuron migration / habituation / astrocyte development / conditioned taste aversion / positive regulation of potassium ion transport / striatum development / dentate gyrus development / maternal behavior / arrestin family protein binding / non-motile cilium / adult walking behavior / mating behavior / long-term synaptic depression / 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 / mu-type opioid receptor binding / developmental growth / corticotropin-releasing hormone receptor 1 binding / G-protein alpha-subunit binding / intracellular transport / D1 dopamine receptor binding / GABA-ergic synapse / neuronal action potential / behavioral fear response / Hedgehog 'off' state / prepulse inhibition / beta-2 adrenergic receptor binding / adenylate cyclase-activating adrenergic receptor signaling pathway / synapse assembly / response to amphetamine / activation of adenylate cyclase activity / adenylate cyclase activator activity / presynaptic modulation of chemical synaptic transmission / positive regulation of synaptic transmission, glutamatergic / 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 / insulin-like growth factor receptor binding / ionotropic glutamate receptor binding / G-protein beta/gamma-subunit complex binding / visual learning / bone development / 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 / adenylate cyclase-activating 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 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / memory / cognition / 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 / cilium / 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 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: 3.13 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 | ||||||||||||||||||||
密度 |
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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 GDP-bound dopamine receptor 1 and mini-G...
全体 | 名称: Cryo-EM structure of the GDP-bound dopamine receptor 1 and mini-Gs complex with Nb35 |
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要素 |
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-超分子 #1: Cryo-EM structure of the GDP-bound dopamine receptor 1 and mini-G...
超分子 | 名称: Cryo-EM structure of the GDP-bound dopamine receptor 1 and mini-Gs complex with Nb35 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: ![]() |
組換発現 | 生物種: ![]() |
-分子 #1: D(1A) dopamine receptor
分子 | 名称: D(1A) dopamine receptor / 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: 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 #2: 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: 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: 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 #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: 39.286891 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: HHHHHHLEVL FQGPGSSGSE LDQLRQEAEQ LKNQIRDARK ACADATLSQI TNNIDPVGRI QMRTRRTLRG HLAKIYAMHW GTDSRLLVS ASQDGKLIIW DSYTTNKVHA IPLRSSWVMT CAYAPSGNYV ACGGLDNICS IYNLKTREGN VRVSRELAGH T GYLSCCRF ...文字列: HHHHHHLEVL FQGPGSSGSE LDQLRQEAEQ LKNQIRDARK ACADATLSQI TNNIDPVGRI QMRTRRTLRG HLAKIYAMHW GTDSRLLVS ASQDGKLIIW DSYTTNKVHA IPLRSSWVMT CAYAPSGNYV ACGGLDNICS IYNLKTREGN VRVSRELAGH T GYLSCCRF LDDNQIVTSS GDTTCALWDI ETGQQTTTFT GHTGDVMSLS LAPDTRLFVS GACDASAKLW DVREGMCRQT FT GHESDIN AICFFPNGNA FATGSDDATC RLFDLRADQE LMTYSHDNII CGITSVSFSK SGRLLLAGYD DFNCNVWDAL KAD RAGVLA GHDNRVSCLG VTDDGMAVAT GSWDSFLKIW N |
-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: Nanobody 35
分子 | 名称: Nanobody 35 / 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: synthetic construct (人工物) |
分子量 | 理論値: 17.352498 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MKYLLPTAAA GLLLLAAQPA MAQVQLQESG GGLVQPGGSL RLSCAASGFT FSNYKMNWVR QAPGKGLEWV SDISQSGASI SYTGSVKGR FTISRDNAKN TLYLQMNSLK PEDTAVYYCA RCPAPFTRDC FDVTSTTYAY RGQGTQVTVS SHHHHHHEPE A |
-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: |
-分子 #7: MAGNESIUM ION
分子 | 名称: MAGNESIUM ION / タイプ: ligand / ID: 7 / コピー数: 1 / 式: MG |
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分子量 | 理論値: 24.305 Da |
-分子 #8: GUANOSINE-5'-DIPHOSPHATE
分子 | 名称: GUANOSINE-5'-DIPHOSPHATE / タイプ: ligand / ID: 8 / コピー数: 1 / 式: GDP |
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分子量 | 理論値: 443.201 Da |
Chemical component information | ![]() ChemComp-GDP: |
-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 / 材質: GOLD / メッシュ: 300 / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY / 前処理 - タイプ: GLOW DISCHARGE |
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) 実像数: 601 / 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 |