+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6k42 | ||||||
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タイトル | cryo-EM structure of alpha2BAR-Gi1 complex | ||||||
要素 |
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キーワード | MEMBRANE PROTEIN / GPCR / Complex / cryo-EM | ||||||
機能・相同性 | 機能・相同性情報 Activation of the phototransduction cascade / Sensory perception of sweet, bitter, and umami (glutamate) taste / regulation of vascular associated smooth muscle contraction / Olfactory Signaling Pathway / negative regulation of uterine smooth muscle contraction / adenylate cyclase-inhibiting adrenergic receptor signaling pathway / phospholipase C-activating adrenergic receptor signaling pathway / alpha2-adrenergic receptor activity / Adrenaline signalling through Alpha-2 adrenergic receptor / G beta:gamma signalling through PLC beta ...Activation of the phototransduction cascade / Sensory perception of sweet, bitter, and umami (glutamate) taste / regulation of vascular associated smooth muscle contraction / Olfactory Signaling Pathway / negative regulation of uterine smooth muscle contraction / adenylate cyclase-inhibiting adrenergic receptor signaling pathway / phospholipase C-activating adrenergic receptor signaling pathway / alpha2-adrenergic receptor activity / Adrenaline signalling through Alpha-2 adrenergic receptor / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / alpha-2C adrenergic receptor binding / receptor transactivation / Prostacyclin signalling through prostacyclin receptor / G alpha (z) signalling events / Glucagon-type ligand receptors / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / epinephrine binding / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / G beta:gamma signalling through BTK / Adenylate cyclase inhibitory pathway / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / alpha-1B adrenergic receptor binding / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thromboxane signalling through TP receptor / positive regulation of uterine smooth muscle contraction / negative regulation of norepinephrine secretion / Thrombin signalling through proteinase activated receptors (PARs) / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Ca2+ pathway / G alpha (s) signalling events / negative regulation of epinephrine secretion / negative regulation of calcium ion transmembrane transporter activity / G alpha (q) signalling events / Extra-nuclear estrogen signaling / G alpha (12/13) signalling events / heterotrimeric G-protein binding / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (i) signalling events / GPER1 signaling / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / dopaminergic synapse / negative regulation of calcium ion-dependent exocytosis / ADP signalling through P2Y purinoceptor 1 / Surfactant metabolism / positive regulation of potassium ion transport / phototransduction, visible light / positive regulation of blood pressure / thermoception / fear response / thioesterase binding / negative regulation of insulin secretion involved in cellular response to glucose stimulus / positive regulation of membrane protein ectodomain proteolysis / Adrenaline,noradrenaline inhibits insulin secretion / norepinephrine binding / alkylglycerophosphoethanolamine phosphodiesterase activity / ADP signalling through P2Y purinoceptor 12 / Adrenoceptors / intestinal absorption / Extra-nuclear estrogen signaling / positive regulation of epidermal growth factor receptor signaling pathway / photoreceptor outer segment membrane / G alpha (i) signalling events / spectrin binding / positive regulation of wound healing / adrenergic receptor signaling pathway / activation of protein kinase activity / negative regulation of calcium ion transport / Rho protein signal transduction / photoreceptor outer segment / regulation of vasoconstriction / GABA-ergic synapse / positive regulation of protein localization to cell cortex / negative regulation of insulin secretion / regulation of cAMP-mediated signaling / negative regulation of lipid catabolic process / G protein-coupled serotonin receptor binding / presynaptic active zone membrane / axon terminus / adenylate cyclase-activating adrenergic receptor signaling pathway / regulation of mitotic spindle organization / viral release from host cell by cytolysis / cellular response to forskolin / cellular response to hormone stimulus / cardiac muscle cell apoptotic process / presynaptic modulation of chemical synaptic transmission / positive regulation of neuron differentiation / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / activation of protein kinase B activity / photoreceptor inner segment / peptidoglycan catabolic process / positive regulation of cytokine production / G protein-coupled receptor binding / G protein-coupled receptor activity / female pregnancy / postsynaptic density membrane 類似検索 - 分子機能 | ||||||
生物種 | Bos taurus (ウシ) Mus musculus (ハツカネズミ) Homo sapiens (ヒト) Enterobacteria phage RB59 (ファージ) | ||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 4.1 Å | ||||||
データ登録者 | Yuan, D. / Liu, Z. / Wang, H.W. / Kobilka, B.K. | ||||||
引用 | ジャーナル: Nat Chem Biol / 年: 2020 タイトル: Activation of the α adrenoceptor by the sedative sympatholytic dexmedetomidine. 著者: Daopeng Yuan / Zhongmin Liu / Jonas Kaindl / Shoji Maeda / Jiawei Zhao / Xiaoou Sun / Jun Xu / Peter Gmeiner / Hong-Wei Wang / Brian K Kobilka / 要旨: The α adrenergic receptors (αARs) are G protein-coupled receptors (GPCRs) that respond to adrenaline and noradrenaline and couple to the Gi/o family of G proteins. αARs play important roles in ...The α adrenergic receptors (αARs) are G protein-coupled receptors (GPCRs) that respond to adrenaline and noradrenaline and couple to the Gi/o family of G proteins. αARs play important roles in regulating the sympathetic nervous system. Dexmedetomidine is a highly selective αAR agonist used in post-operative patients as an anxiety-reducing, sedative medicine that decreases the requirement for opioids. As is typical for selective αAR agonists, dexmedetomidine consists of an imidazole ring and a substituted benzene moiety lacking polar groups, which is in contrast to βAR-selective agonists, which share an ethanolamine group and an aromatic system with polar, hydrogen-bonding substituents. To better understand the structural basis for the selectivity and efficacy of adrenergic agonists, we determined the structure of the αAR in complex with dexmedetomidine and Go at a resolution of 2.9 Å by single-particle cryo-EM. The structure reveals the mechanism of αAR-selective activation and provides insights into Gi/o coupling specificity. | ||||||
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 | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 6k42.cif.gz | 211.1 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6k42.ent.gz | 166.2 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6k42.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
文書・要旨 | 6k42_validation.pdf.gz | 775.6 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 6k42_full_validation.pdf.gz | 781.7 KB | 表示 | |
XML形式データ | 6k42_validation.xml.gz | 34.3 KB | 表示 | |
CIF形式データ | 6k42_validation.cif.gz | 52.8 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/k4/6k42 ftp://data.pdbj.org/pub/pdb/validation_reports/k4/6k42 | HTTPS FTP |
-関連構造データ
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
-Guanine nucleotide-binding protein ... , 3種, 3分子 ABG
#1: タンパク質 | 分子量: 40415.031 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Bos taurus (ウシ) / 遺伝子: GNAI1 / 発現宿主: Spodoptera (蝶・蛾) / 参照: UniProt: P63097 |
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#2: タンパク質 | 分子量: 38530.992 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Mus musculus (ハツカネズミ) / 遺伝子: Gnb1 / 発現宿主: Spodoptera (蝶・蛾) / 参照: UniProt: P62874 |
#3: タンパク質 | 分子量: 7861.143 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNG2 / 発現宿主: Spodoptera (蝶・蛾) / 参照: UniProt: P59768 |
-タンパク質 / 抗体 / 非ポリマー , 3種, 3分子 RH
#4: タンパク質 | 分子量: 58156.211 Da / 分子数: 1 / 由来タイプ: 組換発現 由来: (組換発現) Homo sapiens (ヒト), (組換発現) Enterobacteria phage RB59 (ファージ) 遺伝子: ADRA2A, ADRA2R, ADRAR, e, RB59_126, ADRA2B, ADRA2L1, ADRA2RL1 発現宿主: Spodoptera (蝶・蛾) 参照: UniProt: P08913, UniProt: A0A097J809, UniProt: P18089, lysozyme |
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#5: 抗体 | 分子量: 32898.781 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Mus musculus (ハツカネズミ) / 発現宿主: Spodoptera (蝶・蛾) |
#6: 化合物 | ChemComp-CZX / |
-詳細
研究の焦点であるリガンドがあるか | Y |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: 3D ARRAY / 3次元再構成法: 単粒子再構成法 |
-試料調製
構成要素 | 名称: alpha2BAR-Gi1 complex / タイプ: COMPLEX / Entity ID: #1-#5 / 由来: MULTIPLE SOURCES |
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分子量 | 値: 0.15 MDa / 実験値: YES |
由来(天然) | 生物種: Spodoptera (蝶・蛾) |
緩衝液 | pH: 7.5 |
試料 | 濃度: 10 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
試料支持 | グリッドの材料: GOLD / グリッドのサイズ: 400 divisions/in. / グリッドのタイプ: Quantifoil R1.2/1.3 |
急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 100 % |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: SPOT SCAN |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 電子線照射量: 50 e/Å2 / 検出モード: SUPER-RESOLUTION フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.13_2998: / 分類: 精密化 |
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CTF補正 | タイプ: NONE |
3次元再構成 | 解像度: 4.1 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 235982 / 対称性のタイプ: POINT |