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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 | |||||||||
![]() | alpha2BAR-Gi1 complex | |||||||||
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![]() | GPCR / Complex / cryo-EM / MEMBRANE PROTEIN | |||||||||
機能・相同性 | ![]() Activation of the phototransduction cascade / Olfactory Signaling Pathway / Sensory perception of sweet, bitter, and umami (glutamate) taste / negative regulation of uterine smooth muscle contraction / adenylate cyclase-inhibiting adrenergic receptor signaling pathway / alpha2-adrenergic receptor activity / Adrenaline signalling through Alpha-2 adrenergic receptor / alpha-2C adrenergic receptor binding / phospholipase C-activating adrenergic receptor signaling pathway / : ...Activation of the phototransduction cascade / Olfactory Signaling Pathway / Sensory perception of sweet, bitter, and umami (glutamate) taste / negative regulation of uterine smooth muscle contraction / adenylate cyclase-inhibiting adrenergic receptor signaling pathway / alpha2-adrenergic receptor activity / Adrenaline signalling through Alpha-2 adrenergic receptor / alpha-2C adrenergic receptor binding / phospholipase C-activating adrenergic receptor signaling pathway / : / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / regulation of vascular associated smooth muscle contraction / Prostacyclin signalling through prostacyclin receptor / negative regulation of epinephrine secretion / epinephrine binding / 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 / G beta:gamma signalling through BTK / positive regulation of uterine smooth muscle contraction / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Adenylate cyclase inhibitory pathway / Thromboxane signalling through TP receptor / negative regulation of norepinephrine secretion / alpha-1B adrenergic receptor binding / Thrombin signalling through proteinase activated receptors (PARs) / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / negative regulation of calcium ion transmembrane transporter activity / G-protein activation / G alpha (s) signalling events / G alpha (12/13) signalling events / Ca2+ pathway / G alpha (q) signalling events / Extra-nuclear estrogen signaling / heterotrimeric G-protein binding / Vasopressin regulates renal water homeostasis via Aquaporins / GPER1 signaling / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / negative regulation of calcium ion-dependent exocytosis / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / ADP signalling through P2Y purinoceptor 1 / activation of protein kinase activity / dopaminergic synapse / Surfactant metabolism / positive regulation of blood pressure / thermoception / positive regulation of potassium ion transport / fear response / thioesterase binding / negative regulation of insulin secretion involved in cellular response to glucose stimulus / response to alcohol / positive regulation of membrane protein ectodomain proteolysis / norepinephrine binding / intestinal absorption / Adrenoceptors / 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 / G alpha (i) signalling events / spectrin binding / adrenergic receptor signaling pathway / alkylglycerophosphoethanolamine phosphodiesterase activity / negative regulation of calcium ion transport / phototransduction, visible light / photoreceptor outer segment / Rho protein signal transduction / regulation of vasoconstriction / negative regulation of lipid catabolic process / negative regulation of insulin secretion / cellular response to hormone stimulus / viral release from host cell by cytolysis / positive regulation of protein localization to cell cortex / activation of protein kinase B activity / adenylate cyclase-activating adrenergic receptor signaling pathway / presynaptic active zone membrane / G protein-coupled serotonin receptor binding / axon terminus / cardiac muscle cell apoptotic process / presynaptic modulation of chemical synaptic transmission / peptidoglycan catabolic process / cellular response to forskolin / positive regulation of MAP kinase activity / positive regulation of neuron differentiation / regulation of mitotic spindle organization / guanyl-nucleotide exchange factor activity / positive regulation of cytokine production / GABA-ergic synapse / female pregnancy / G protein-coupled receptor binding / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway 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: 4.1 Å | |||||||||
![]() | Yuan D / Liu Z | |||||||||
![]() | ![]() 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
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構造ビューア | EMマップ: ![]() ![]() ![]() |
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マップデータ | ![]() | 3.4 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 15.7 KB 15.7 KB | 表示 表示 | ![]() |
画像 | ![]() | 48.3 KB | ||
Filedesc metadata | ![]() | 6.4 KB | ||
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「今月の分子」の関連する項目 |
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ファイル | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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
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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: ![]() |
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 |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 40.415031 KDa |
組換発現 | 生物種: ![]() |
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 |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 38.530992 KDa |
組換発現 | 生物種: ![]() |
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: ![]() |
分子量 | 理論値: 7.861143 KDa |
組換発現 | 生物種: ![]() |
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: ![]() |
分子量 | 理論値: 58.156211 KDa |
組換発現 | 生物種: ![]() |
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 |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 32.898781 KDa |
組換発現 | 生物種: ![]() |
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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![]() | 単粒子再構成法 |
試料の集合状態 | 3D array |
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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 |
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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 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: ![]() |
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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画像解析
初期モデル | モデルのタイプ: PDB ENTRY |
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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 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |