+ データを開く
データを開く
- 基本情報
基本情報
| 登録情報 | データベース: EMDB / ID: EMD-9912 | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| タイトル | cryo-EM structure of alpha2BAR-Gi1 complex | |||||||||
|  マップデータ | alpha2BAR-Gi1 complex | |||||||||
|  試料 | 
 | |||||||||
|  キーワード | GPCR / Complex / cryo-EM / MEMBRANE PROTEIN | |||||||||
| 機能・相同性 |  機能・相同性情報 Activation of the phototransduction cascade / Olfactory Signaling Pathway / negative regulation of uterine smooth muscle contraction / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / adenylate cyclase-inhibiting adrenergic receptor signaling pathway / Prostacyclin signalling through prostacyclin receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / alpha2-adrenergic receptor activity / Adrenaline signalling through Alpha-2 adrenergic receptor ...Activation of the phototransduction cascade / Olfactory Signaling Pathway / negative regulation of uterine smooth muscle contraction / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / adenylate cyclase-inhibiting adrenergic receptor signaling pathway / Prostacyclin signalling through prostacyclin receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / alpha2-adrenergic receptor activity / Adrenaline signalling through Alpha-2 adrenergic receptor / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / G alpha (z) signalling events / Glucagon-type ligand receptors / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / alpha-2C adrenergic receptor binding / epinephrine binding / positive regulation of uterine smooth muscle contraction / Adrenaline,noradrenaline inhibits insulin secretion / phospholipase C-activating adrenergic receptor signaling pathway / ADP signalling through P2Y purinoceptor 12 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / G beta:gamma signalling through BTK / Adenylate cyclase inhibitory pathway / Thromboxane signalling through TP receptor / Thrombin signalling through proteinase activated receptors (PARs) / alpha-1B adrenergic receptor binding / Activation of G protein gated Potassium channels / Inhibition  of voltage gated Ca2+ channels via Gbeta/gamma subunits / negative regulation of norepinephrine secretion / G-protein activation / G alpha (s) signalling events / negative regulation of epinephrine secretion / Ca2+ pathway / G alpha (12/13) signalling events / Extra-nuclear estrogen signaling / G alpha (q) signalling events / Vasopressin regulates renal water homeostasis via Aquaporins / GPER1 signaling / regulation of vascular associated smooth muscle contraction / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / heterotrimeric G-protein binding / G alpha (i) signalling events / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / ADP signalling through P2Y purinoceptor 1 / negative regulation of calcium ion-dependent exocytosis / positive regulation of blood pressure / Surfactant metabolism / positive regulation of potassium ion transport / dopaminergic synapse / thermoception / fear response / thioesterase binding / negative regulation of insulin secretion involved in cellular response to glucose stimulus / positive regulation of membrane protein ectodomain proteolysis / norepinephrine binding / Adrenoceptors / response to alcohol / intestinal absorption / ADP signalling through P2Y purinoceptor 12 / Adrenaline,noradrenaline inhibits insulin secretion / positive regulation of epidermal growth factor receptor signaling pathway / Extra-nuclear estrogen signaling / response to morphine / positive regulation of wound healing / adrenergic receptor signaling pathway / spectrin binding / G alpha (i) signalling events / alkylglycerophosphoethanolamine phosphodiesterase activity / negative regulation of calcium ion transport / phototransduction, visible light / photoreceptor outer segment / regulation of vasoconstriction / negative regulation of lipid catabolic process / viral release from host cell by cytolysis / cellular response to hormone stimulus / positive regulation of protein localization to cell cortex / Rho protein signal transduction / adenylate cyclase-activating adrenergic receptor signaling pathway / G protein-coupled serotonin receptor binding / presynaptic active zone membrane / axon terminus / peptidoglycan catabolic process / cardiac muscle cell apoptotic process / positive regulation of neuron differentiation / presynaptic modulation of chemical synaptic transmission / cellular response to forskolin / regulation of mitotic spindle organization / guanyl-nucleotide exchange factor activity / positive regulation of cytokine production / female pregnancy / negative regulation of insulin secretion / G protein-coupled receptor binding / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / postsynaptic density membrane / GABA-ergic synapse / platelet activation / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / vasodilation 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 | |||||||||
|  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
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:  SurfView  Molmil  Jmol/JSmol | 
| 添付画像 | 
- ダウンロードとリンク
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 | 19.2 KB 19.2 KB | 表示 表示 |  EMDBヘッダ | 
| 画像 |  emd_9912.png | 48.3 KB | ||
| Filedesc metadata |  emd-9912.cif.gz | 7.1 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 | 337.2 KB | 表示 |  EMDB検証レポート | 
|---|---|---|---|---|
| 文書・詳細版 |  emd_9912_full_validation.pdf.gz | 336.8 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 | 6.8 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
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
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
試料の構成要素
-全体 : alpha2BAR-Gi1 complex
| 全体 | 名称: alpha2BAR-Gi1 complex | 
|---|---|
| 要素 | 
 | 
-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 | 理論値: 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 | 
|---|---|
| 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 UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1 | 
-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 | 
|---|---|
| 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 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: 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 UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 | 
-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 UniProtKB: Alpha-2A adrenergic receptor, Endolysin, Alpha-2B adrenergic receptor, Alpha-2B adrenergic receptor | 
-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 | 
|---|---|
| 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 | 
|---|---|
|  解析 | 単粒子再構成法 | 
| 試料の集合状態 | 3D array | 
- 試料調製
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
電子顕微鏡法
| 顕微鏡 | FEI TITAN KRIOS | 
|---|---|
| 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 | 
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