+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-9912 | |||||||||
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タイトル | cryo-EM structure of alpha2BAR-Gi1 complex | |||||||||
マップデータ | alpha2BAR-Gi1 complex | |||||||||
試料 |
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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 / cellular response to forskolin / viral release from host cell by cytolysis / 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 | Spodoptera (蝶・蛾) / Bos taurus (ウシ) / Mus musculus (ハツカネズミ) / 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: 4.1 Å | |||||||||
データ登録者 | Yuan D / Liu Z / Wang HW / Kobilka BK | |||||||||
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 | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_9912.map.gz | 3.4 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-9912-v30.xml emd-9912.xml | 15.3 KB 15.3 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_9912.png | 48.3 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-9912 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-9912 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_9912_validation.pdf.gz | 312.9 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_9912_full_validation.pdf.gz | 312.4 KB | 表示 | |
XML形式データ | emd_9912_validation.xml.gz | 5.9 KB | 表示 | |
CIF形式データ | emd_9912_validation.cif.gz | 6.7 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9912 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9912 | HTTPS FTP |
-関連構造データ
-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_9912.map.gz / 形式: CCP4 / 大きさ: 52.7 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | alpha2BAR-Gi1 complex | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: 1.401 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-試料の構成要素
-全体 : alpha2BAR-Gi1 complex
全体 | 名称: alpha2BAR-Gi1 complex |
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要素 |
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-超分子 #1: alpha2BAR-Gi1 complex
超分子 | 名称: alpha2BAR-Gi1 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: Spodoptera (蝶・蛾) |
分子量 | 実験値: 150 KDa |
-分子 #1: Guanine nucleotide-binding protein G(i) subunit alpha-1
分子 | 名称: Guanine nucleotide-binding protein G(i) subunit alpha-1 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: Bos taurus (ウシ) |
分子量 | 理論値: 40.415031 KDa |
組換発現 | 生物種: Spodoptera (蝶・蛾) |
配列 | 文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTTGIVETH FTFKDLHFKM FDVGGQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHESM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY PEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCA TDTKNVQFVF DAVTDVIIKN NLKDCGLF |
-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: Mus musculus (ハツカネズミ) |
分子量 | 理論値: 38.530992 KDa |
組換発現 | 生物種: Spodoptera (蝶・蛾) |
配列 | 文字列: HHHHHHGSSG QSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKL IIWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC R FLDDNQIV ...文字列: HHHHHHGSSG QSELDQLRQE 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 KIWN |
-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: 7.861143 KDa |
組換発現 | 生物種: Spodoptera (蝶・蛾) |
配列 | 文字列: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L |
-分子 #4: Alpha-2A adrenergic receptor,Endolysin,Alpha-2B adrenergic recept...
分子 | 名称: Alpha-2A adrenergic receptor,Endolysin,Alpha-2B adrenergic receptor,Alpha-2B adrenergic receptor タイプ: protein_or_peptide / ID: 4 / コピー数: 1 / 光学異性体: LEVO / EC番号: lysozyme |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 58.156211 KDa |
組換発現 | 生物種: Spodoptera (蝶・蛾) |
配列 | 文字列: DDDDAHHHHH HMGSLQPDAG NASWNGTEAP GGGARATPEN LYFQGNIFEM LRIDEGLRLK IYKDTEGYYT IGIGHLLTKS PSLNAAKSE LDKAIGRNTN GVITKDEAEK LFNQDVDAAV RGILRNAKLK PVYDSLDAVR RAALINMVFQ MGETGVAGFT N SLRMLQQK ...文字列: DDDDAHHHHH HMGSLQPDAG NASWNGTEAP GGGARATPEN LYFQGNIFEM LRIDEGLRLK IYKDTEGYYT IGIGHLLTKS PSLNAAKSE LDKAIGRNTN GVITKDEAEK LFNQDVDAAV RGILRNAKLK PVYDSLDAVR RAALINMVFQ MGETGVAGFT N SLRMLQQK RWDEAAVNLA KSRWYNQTPN RAKRVITTFR TGTWDAYYSV QATAAIAAAI TFLILFTIFG NALVILAVLT SR SLRAPQN LFLVSLAAAD ILVATLIIPF SLANELLGYW YFRRTWCEVY LALDVLFCTS SIVHLCAISL DRYWAVSRAL EYN SKRTPR RIKCIILTVW LIAAVISLPP LIYKGDQGPQ PRGRPQCKLN QEAWYILASS IGSFFAPCLI MILVYLRIYL IAKR SNRRG PRAKGGPGQG EQWWRRRAQL TREKRFTFVL AVVIGVFVLC WFPFFFSYSL GAICPKHCKV PHGLFQFFFW IGYCN SSLN PVIYTIFNQD FRRAFRRILC RPWTQTAW |
-分子 #5: scFv
分子 | 名称: scFv / 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: Mus musculus (ハツカネズミ) |
分子量 | 理論値: 32.898781 KDa |
組換発現 | 生物種: Spodoptera (蝶・蛾) |
配列 | 文字列: MLLVNQSHQG FNKEHTSKMV SAIVLYVLLA AAAHSAFADV QLVESGGGLV QPGGSRKLSC SASGFAFSSF GMHWVRQAPE KGLEWVAYI SSGSGTIYYA DTVKGRFTIS RDDPKNTLFL QMTSLRSEDT AMYYCVRSIY YYGSSPFDFW GQGTTLTVSS G GGGSGGGG ...文字列: MLLVNQSHQG FNKEHTSKMV SAIVLYVLLA AAAHSAFADV QLVESGGGLV QPGGSRKLSC SASGFAFSSF GMHWVRQAPE KGLEWVAYI SSGSGTIYYA DTVKGRFTIS RDDPKNTLFL QMTSLRSEDT AMYYCVRSIY YYGSSPFDFW GQGTTLTVSS G GGGSGGGG SGGGGSDIVM TQATSSVPVT PGESVSISCR SSKSLLHSNG NTYLYWFLQR PGQSPQLLIY RMSNLASGVP DR FSGSGSG TAFTLTISRL EAEDVGVYYC MQHLEYPLTF GAGTKLELKG SLEVLFQGPA AAHHHHHHHH |
-分子 #6: 4-[(1~{S})-1-(2,3-dimethylphenyl)ethyl]-1~{H}-imidazole
分子 | 名称: 4-[(1~{S})-1-(2,3-dimethylphenyl)ethyl]-1~{H}-imidazole タイプ: ligand / ID: 6 / コピー数: 1 / 式: CZX |
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分子量 | 理論値: 200.28 Da |
Chemical component information | ChemComp-CZX: |
-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 | 3D array |
-試料調製
濃度 | 10 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: 400 |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / 装置: FEI VITROBOT MARK IV |
-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 K2 SUMMIT (4k x 4k) 検出モード: SUPER-RESOLUTION / 平均電子線量: 50.0 e/Å2 |
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: SPOT SCAN / 撮影モード: BRIGHT FIELD |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 4.1 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 235982 |
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初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |