+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-21669 | |||||||||
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タイトル | HTR2A bound to 25-CN-NBOH in complex with a mini-Galpha-q protein, beta/gamma subunits and an active-state stabilizing single-chain variable fragment (scFv16) obtained by cryo-electron microscopy (cryoEM) | |||||||||
マップデータ | HTR2A bound to 25-CN-NBOH in complex with a mini-G%u237Aq protein, %u03B2/%uD835%uDEFE subunits and an active-state stabilizing single-chain variable fragment (scFv16) obtained by cryo-electron microscopy (cryoEM) | |||||||||
試料 |
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機能・相同性 | 機能・相同性情報 protein localization to cytoskeleton / 1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding / Gq/11-coupled serotonin receptor activity / phospholipase C-activating serotonin receptor signaling pathway / positive regulation of phosphatidylinositol biosynthetic process / G protein-coupled serotonin receptor signaling pathway / G protein-coupled serotonin receptor complex / serotonin receptor signaling pathway / artery smooth muscle contraction / セロトニン受容体 ...protein localization to cytoskeleton / 1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding / Gq/11-coupled serotonin receptor activity / phospholipase C-activating serotonin receptor signaling pathway / positive regulation of phosphatidylinositol biosynthetic process / G protein-coupled serotonin receptor signaling pathway / G protein-coupled serotonin receptor complex / serotonin receptor signaling pathway / artery smooth muscle contraction / セロトニン受容体 / cell body fiber / urinary bladder smooth muscle contraction / serotonin binding / negative regulation of synaptic transmission, glutamatergic / G protein-coupled serotonin receptor activity / neurotransmitter receptor activity / temperature homeostasis / regulation of dopamine secretion / protein tyrosine kinase activator activity / behavioral response to cocaine / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / detection of temperature stimulus involved in sensory perception of pain / negative regulation of potassium ion transport / activation of phospholipase C activity / positive regulation of fat cell differentiation / detection of mechanical stimulus involved in sensory perception of pain / release of sequestered calcium ion into cytosol / positive regulation of vasoconstriction / presynaptic modulation of chemical synaptic transmission / positive regulation of glycolytic process / dendritic shaft / phosphatidylinositol 3-kinase/protein kinase B signal transduction / カベオラ / glycolytic process / 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 / 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 / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / 記憶 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / intracellular calcium ion homeostasis / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / adenylate cyclase-activating dopamine receptor signaling pathway / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / sensory perception of taste / GPER1 signaling / G-protein beta-subunit binding / positive regulation of neuron apoptotic process / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / positive regulation of peptidyl-tyrosine phosphorylation / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / virus receptor activity / retina development in camera-type eye / presynaptic membrane / GTPase binding / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (i) signalling events / positive regulation of cytosolic calcium ion concentration / fibroblast proliferation / G alpha (s) signalling events / cytoplasmic vesicle / chemical synaptic transmission / G alpha (q) signalling events / postsynaptic membrane / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / electron transfer activity / ペリプラズム / positive regulation of ERK1 and ERK2 cascade / response to xenobiotic stimulus / iron ion binding / G protein-coupled receptor signaling pathway / lysosomal membrane 類似検索 - 分子機能 | |||||||||
生物種 | 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: 3.36 Å | |||||||||
データ登録者 | Skiniotis G / Roth B / Kim K / Panova O | |||||||||
資金援助 | 米国, 2件
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引用 | ジャーナル: Cell / 年: 2020 タイトル: Structure of a Hallucinogen-Activated Gq-Coupled 5-HT Serotonin Receptor. 著者: Kuglae Kim / Tao Che / Ouliana Panova / Jeffrey F DiBerto / Jiankun Lyu / Brian E Krumm / Daniel Wacker / Michael J Robertson / Alpay B Seven / David E Nichols / Brian K Shoichet / Georgios ...著者: Kuglae Kim / Tao Che / Ouliana Panova / Jeffrey F DiBerto / Jiankun Lyu / Brian E Krumm / Daniel Wacker / Michael J Robertson / Alpay B Seven / David E Nichols / Brian K Shoichet / Georgios Skiniotis / Bryan L Roth / 要旨: Hallucinogens like lysergic acid diethylamide (LSD), psilocybin, and substituted N-benzyl phenylalkylamines are widely used recreationally with psilocybin being considered as a therapeutic for many ...Hallucinogens like lysergic acid diethylamide (LSD), psilocybin, and substituted N-benzyl phenylalkylamines are widely used recreationally with psilocybin being considered as a therapeutic for many neuropsychiatric disorders including depression, anxiety, and substance abuse. How psychedelics mediate their actions-both therapeutic and hallucinogenic-are not understood, although activation of the 5-HT serotonin receptor (HTR2A) is key. To gain molecular insights into psychedelic actions, we determined the active-state structure of HTR2A bound to 25-CN-NBOH-a prototypical hallucinogen-in complex with an engineered Gαq heterotrimer by cryoelectron microscopy (cryo-EM). We also obtained the X-ray crystal structures of HTR2A complexed with the arrestin-biased ligand LSD or the inverse agonist methiothepin. Comparisons of these structures reveal determinants responsible for HTR2A-Gαq protein interactions as well as the conformational rearrangements involved in active-state transitions. Given the potential therapeutic actions of hallucinogens, these findings could accelerate the discovery of more selective drugs for the treatment of a variety of neuropsychiatric disorders. | |||||||||
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_21669.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-21669-v30.xml emd-21669.xml | 19.6 KB 19.6 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_21669.png | 44.8 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-21669 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-21669 | 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_21669.map.gz / 形式: CCP4 / 大きさ: 28.7 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | HTR2A bound to 25-CN-NBOH in complex with a mini-G%u237Aq protein, %u03B2/%uD835%uDEFE subunits and an active-state stabilizing single-chain variable fragment (scFv16) obtained by cryo-electron microscopy (cryoEM) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.8521 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 : HTR2A bound to 25-CN-NBOH in complex with a mini-Galpha-q protein...
全体 | 名称: HTR2A bound to 25-CN-NBOH in complex with a mini-Galpha-q protein, beta/gamma subunits and an active-state stabilizing single-chain variable fragment (scFv16) obtained by cryo-electron microscopy (cryoEM) |
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要素 |
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-超分子 #1: HTR2A bound to 25-CN-NBOH in complex with a mini-Galpha-q protein...
超分子 | 名称: HTR2A bound to 25-CN-NBOH in complex with a mini-Galpha-q protein, beta/gamma subunits and an active-state stabilizing single-chain variable fragment (scFv16) obtained by cryo-electron microscopy (cryoEM) 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: Homo sapiens (ヒト) |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
-分子 #1: Soluble cytochrome b562,5-hydroxytryptamine receptor 2A chimera
分子 | 名称: Soluble cytochrome b562,5-hydroxytryptamine receptor 2A chimera 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: Homo sapiens (ヒト) |
分子量 | 理論値: 56.167309 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MKTIIALSYI FCLVFADYKD DDDAKLQTMH HHHHHHHHHE NLYFQGGTTM ADLEDNWETL NDNLKVIEKA DNAAQVKDAL TKMRAAALD AQKATPPKLE DKSPDSPEMK DFRHGFDILV GQIDDALKLA NEGKVKEAQA AAEQLKTTRN AYIQKYLGSL S LLHLQEKN ...文字列: MKTIIALSYI FCLVFADYKD DDDAKLQTMH HHHHHHHHHE NLYFQGGTTM ADLEDNWETL NDNLKVIEKA DNAAQVKDAL TKMRAAALD AQKATPPKLE DKSPDSPEMK DFRHGFDILV GQIDDALKLA NEGKVKEAQA AAEQLKTTRN AYIQKYLGSL S LLHLQEKN WSALLTAVVI ILTIAGNILV IMAVSLEKKL QNATNYFLMS LAIADMLLGF LVMPVSMLTI LYGYRWPLPS KL CAVWIYL DVLFSTASIM HLCAISLDRY VAIQNPIHHS RFNSRTKAFL KIIAVWTISV GISMPIPVFG LQDDSKVFKE GSC LLADDN FVLIGSFVSF FIPLTIMVIT YFLTIKSLQK EATLCVSDLG TRAKLASFSF LPQSSLSSEK LFQRSIHREP GSYT GRRTM QSISNEQKAC KVLGIVFFLF VVMWCPFFIT NIMAVICKES CNEDVIGALL NVFVWIGYLS SAVNPLVYTL FNKTY RSAF SRYIQCQYKE NKK |
-分子 #2: G subunit q (Gi2-mini-Gq chimeric)
分子 | 名称: G subunit q (Gi2-mini-Gq chimeric) / 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: Homo sapiens (ヒト) |
分子量 | 理論値: 28.084832 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MGSTVSAEDK AAAERSKMID KNLREDGEKA RRTLRLLLLG ADNSGKSTIV KQMRILHGGS GGSGGTSGIF ETKFQVDKVN FHMFDVGGQ RDERRKWIQC FNDVTAIIFV VDSSDYNRLQ EALNDFKSIW NNRWLRTISV ILFLNKQDLL AEKVLAGKSK I EDYFPEFA ...文字列: MGSTVSAEDK AAAERSKMID KNLREDGEKA RRTLRLLLLG ADNSGKSTIV KQMRILHGGS GGSGGTSGIF ETKFQVDKVN FHMFDVGGQ RDERRKWIQC FNDVTAIIFV VDSSDYNRLQ EALNDFKSIW NNRWLRTISV ILFLNKQDLL AEKVLAGKSK I EDYFPEFA RYTTPEDATP EPGEDPRVTR AKYFIRKEFV DISTASGDGR HICYPHFTCA VDTENARRIF NDCKDIILQM NL REYNLV |
-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: Homo sapiens (ヒト) |
分子量 | 理論値: 39.418086 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MHHHHHHLEV LFQGPGSSGS ELDQLRQEAE QLKNQIRDAR KACADATLSQ ITNNIDPVGR IQMRTRRTLR GHLAKIYAMH WGTDSRLLV SASQDGKLII WDSYTTNKVH AIPLRSSWVM TCAYAPSGNY VACGGLDNIC SIYNLKTREG NVRVSRELAG H TGYLSCCR ...文字列: MHHHHHHLEV LFQGPGSSGS ELDQLRQEAE QLKNQIRDAR KACADATLSQ ITNNIDPVGR IQMRTRRTLR GHLAKIYAMH WGTDSRLLV SASQDGKLII WDSYTTNKVH AIPLRSSWVM TCAYAPSGNY VACGGLDNIC SIYNLKTREG NVRVSRELAG H TGYLSCCR FLDDNQIVTS SGDTTCALWD IETGQQTTTF TGHTGDVMSL SLAPDTRLFV SGACDASAKL WDVREGMCRQ TF TGHESDI NAICFFPNGN AFATGSDDAT CRLFDLRADQ ELMTYSHDNI ICGITSVSFS KSGRLLLAGY DDFNCNVWDA LKA DRAGVL AGHDNRVSCL GVTDDGMAVA TGSWDSFLKI WN |
-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: Homo sapiens (ヒト) |
分子量 | 理論値: 7.861143 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L |
-分子 #5: single Fab chain (svFv16)
分子 | 名称: single Fab chain (svFv16) / 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: Homo sapiens (ヒト) |
分子量 | 理論値: 28.668922 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS ...文字列: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS NGNTYLYWFL QRPGQSPQLL IYRMSNLASG VPDRFSGSGS GTAFTLTISR LEAEDVGVYY CMQHLEYPLT FG AGTKLEL KAAALEVLFQ GPHHHHHHHH |
-分子 #6: 4-(2-{[(2-hydroxyphenyl)methyl]amino}ethyl)-2,5-dimethoxybenzonitrile
分子 | 名称: 4-(2-{[(2-hydroxyphenyl)methyl]amino}ethyl)-2,5-dimethoxybenzonitrile タイプ: ligand / ID: 6 / コピー数: 1 / 式: U0G |
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分子量 | 理論値: 312.363 Da |
Chemical component information | ChemComp-U0G: |
-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 | particle |
-試料調製
濃度 | 16.7 mg/mL | ||||||||||||||||||
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緩衝液 | pH: 7.5 構成要素:
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グリッド | モデル: Quantifoil R1.2/1.3 / 材質: GOLD / 支持フィルム - 材質: CARBON / 前処理 - タイプ: GLOW DISCHARGE | ||||||||||||||||||
凍結 | 凍結剤: ETHANE / 装置: FEI VITROBOT MARK II |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | C2レンズ絞り径: 70.0 µm / 最大 デフォーカス(補正後): 2.5 µm / 最小 デフォーカス(補正後): 1.0 µm / 倍率(補正後): 57050 / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 撮影したグリッド数: 1 / 実像数: 2368 / 平均露光時間: 4.0 sec. / 平均電子線量: 80.0 e/Å2 |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
粒子像選択 | 選択した数: 2712613 |
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CTF補正 | ソフトウェア - 名称: Gctf |
初期 角度割当 | タイプ: OTHER |
最終 3次元分類 | クラス数: 3 |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 再構成 | 使用したクラス数: 1 / 想定した対称性 - 点群: C1 (非対称) / 解像度のタイプ: BY AUTHOR / 解像度: 3.36 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 166497 |