+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-36409 | |||||||||
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タイトル | ST1936-5HT6R complex | |||||||||
マップデータ | This is the cryo-EM density of ST1936-ht6 complex. | |||||||||
試料 |
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キーワード | GPCR / MEMBRANE PROTEIN | |||||||||
機能・相同性 | 機能・相同性情報 histamine receptor activity / Serotonin receptors / G protein-coupled serotonin receptor activity / neurotransmitter receptor activity / cerebral cortex cell migration / PKA activation in glucagon signalling / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / hair follicle placode formation / mu-type opioid receptor binding / developmental growth ...histamine receptor activity / Serotonin receptors / G protein-coupled serotonin receptor activity / neurotransmitter receptor activity / cerebral cortex cell migration / PKA activation in glucagon signalling / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / hair follicle placode formation / mu-type opioid receptor binding / developmental growth / corticotropin-releasing hormone receptor 1 binding / positive regulation of TOR signaling / intracellular transport / D1 dopamine receptor binding / Hedgehog 'off' state / beta-2 adrenergic receptor binding / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / adenylate cyclase activator activity / trans-Golgi network membrane / ionotropic glutamate receptor binding / insulin-like growth factor receptor binding / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / bone development / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G-protein activation / adenylate cyclase-activating G protein-coupled receptor signaling pathway / 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 / cognition / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / cilium / photoreceptor disc membrane / platelet aggregation / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / sensory perception of smell / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / positive regulation of cold-induced thermogenesis / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / chemical synaptic transmission / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / dendrite / protein-containing complex binding / GTP binding / signal transduction / extracellular exosome / membrane / metal ion binding / plasma membrane / cytoplasm / cytosol 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / Camelus bactrianus (フタコブラクダ) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.09 Å | |||||||||
データ登録者 | Wen X / Sun J | |||||||||
資金援助 | 中国, 1件
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引用 | ジャーナル: Biochem Biophys Res Commun / 年: 2023 タイトル: Structural insight into the selective agonist ST1936 binding of serotonin receptor 5-HT6. 著者: Yuan Pei / Xin Wen / Sheng-Chao Guo / Zhi-Shuai Yang / Ru Zhang / Peng Xiao / Jin-Peng Sun / 要旨: The serotonin receptor 5-HTR is an important G-protein-coupled receptor (GPCR) that involved in essential functions within the central and peripheral nervous systems and is linked to various ...The serotonin receptor 5-HTR is an important G-protein-coupled receptor (GPCR) that involved in essential functions within the central and peripheral nervous systems and is linked to various psychiatric disorders. Selective activation of 5-HTR promotes neural stem cell regeneration activity. As a 5-HTR selective agonist, 2-(5 chloro-2-methyl-1H-indol-3-yl)-N, N-dimethylethanolamine (ST1936) has been widely used to investigate the functions of the 5-HTR. The molecular mechanism of how ST1936 is recognized by 5-HTR and how it effectively couples with Gs remain unclear. Here, we reconstituted the ST1936-5-HTR-Gs complex in vitro and solved its cryo-electron microscopy structure at 3.1 Å resolution. Further structural analysis and mutational studies facilitated us to identify the residues of the Y310 and "toggle switch" W281 of the 5-HTR contributed to the higher efficacy of ST1936 compared with 5-HT. By uncovering the structural foundation of how 5-HTR specifically recognizes agonists and elucidating the molecular process of G protein activation, our discoveries offer valuable insights and pave the way for the development of promising 5-HTR agonists. | |||||||||
履歴 |
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-構造の表示
添付画像 |
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-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_36409.map.gz | 27.3 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-36409-v30.xml emd-36409.xml | 18.8 KB 18.8 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_36409.png | 20 KB | ||
その他 | emd_36409_half_map_1.map.gz emd_36409_half_map_2.map.gz | 23.4 MB 23.4 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-36409 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36409 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_36409_validation.pdf.gz | 687.8 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_36409_full_validation.pdf.gz | 687.4 KB | 表示 | |
XML形式データ | emd_36409_validation.xml.gz | 10.4 KB | 表示 | |
CIF形式データ | emd_36409_validation.cif.gz | 11.9 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36409 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36409 | HTTPS FTP |
-関連構造データ
関連構造データ | 8jlzMC M: このマップから作成された原子モデル C: 同じ文献を引用 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-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_36409.map.gz / 形式: CCP4 / 大きさ: 30.5 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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注釈 | This is the cryo-EM density of ST1936-ht6 complex. | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.85 Å | ||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-ハーフマップ: This is the half1 map.
ファイル | emd_36409_half_map_1.map | ||||||||||||
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注釈 | This is the half1 map. | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: This is the half2 map.
ファイル | emd_36409_half_map_2.map | ||||||||||||
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注釈 | This is the half2 map. | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
-全体 : st1936-HT6
全体 | 名称: st1936-HT6 |
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要素 |
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-超分子 #1: st1936-HT6
超分子 | 名称: st1936-HT6 / 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) |
-分子 #1: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
分子 | 名称: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short 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: 45.683434 KDa |
組換発現 | 生物種: Baculovirus expression vector pFastBac1-HM (ウイルス) |
配列 | 文字列: MGCLGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGAGE SGKNTIVKQM RILHVNGFNG EGGEEDPQAA RSNSDGEKA TKVQDIKNNL KEAIETIVAA MSNLVPPVEL ANPENQFRVD YILSVMNVPD FDFPPEFYEH AKALWEDEGV R ACYERSNE ...文字列: MGCLGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGAGE SGKNTIVKQM RILHVNGFNG EGGEEDPQAA RSNSDGEKA TKVQDIKNNL KEAIETIVAA MSNLVPPVEL ANPENQFRVD YILSVMNVPD FDFPPEFYEH AKALWEDEGV R ACYERSNE YQLIDCAQYF LDKIDVIKQA DYVPSDQDLL RCRVLTSGIF ETKFQVDKVN FHMFDVGAQR DERRKWIQCF ND VTAIIFV VASSSYNMVI REDNQTNRLQ AALKLFDSIW NNKWLRDTSV ILFLNKQDLL AEKVLAGKSK IEDYFPEFAR YTT PEDATP EPGEDPRVTR AKYFIRDEFL RISTASGDGR HYCYPHFTCA VDTENIRRVF NDCRDIIQRM HLRQYELL |
-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: Homo sapiens (ヒト) |
分子量 | 理論値: 39.418086 KDa |
組換発現 | 生物種: Baculovirus expression vector pFastBac1-HM (ウイルス) |
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 #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: 6.375332 KDa |
組換発現 | 生物種: Baculovirus expression vector pFastBac1-HM (ウイルス) |
配列 | 文字列: NTASIAQARK LVEQLKMEAN IDRIKVSKAA ADLMAYCEAH AKEDPLLTPV PASENPFR |
-分子 #4: Nb35
分子 | 名称: Nb35 / 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: Camelus bactrianus (フタコブラクダ) |
分子量 | 理論値: 13.885439 KDa |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: QVQLQESGGG LVQPGGSLRL SCAASGFTFS NYKMNWVRQA PGKGLEWVSD ISQSGASISY TGSVKGRFTI SRDNAKNTLY LQMNSLKPE DTAVYYCARC PAPFTRDCFD VTSTTYAYRG QGTQVTVSS |
-分子 #5: 5-hydroxytryptamine receptor 6
分子 | 名称: 5-hydroxytryptamine receptor 6 / 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: 46.99209 KDa |
組換発現 | 生物種: Baculovirus expression vector pFastBac1-HM (ウイルス) |
配列 | 文字列: MVPEPGPTAN STPAWGAGPP SAPGGSGWVA AALCVVIALT AAANSLLIAL ICTQPALRNT SNFFLVSLFT SDLMVGLVVM PPAMLNALY GRWVLARGLC LLWTAFDVMC CSASILNLCL ISLDRYLLIL SPLRYKLRMT PLRALALVLG AWSLAALASF L PLLLGWHE ...文字列: MVPEPGPTAN STPAWGAGPP SAPGGSGWVA AALCVVIALT AAANSLLIAL ICTQPALRNT SNFFLVSLFT SDLMVGLVVM PPAMLNALY GRWVLARGLC LLWTAFDVMC CSASILNLCL ISLDRYLLIL SPLRYKLRMT PLRALALVLG AWSLAALASF L PLLLGWHE LGHARPPVPG QCRLLASLPF VLVASGLTFF LPSGAICFTY CRILLAARKQ AVQVASLTTG MASQASETLQ VP RTPRPGV ESADSRRLAT KHSRKALKAS LTLGILLGMF FVTWLPFFVA NIVQAVCDCI SPGLFDVLTW LGYCNSTMNP IIY PLFMRD FKRALGRFLP CPRCPRERQA SLASPSLRTS HSGPRPGLSL QQVLPLPLPP DSDSDSDAGS GGSSGLRLTA QLLL PGEAT QDPPLPTRAA AAVNFFNIDP AEPELRPHPL GIPTN |
-分子 #6: 2-(5-chloranyl-2-methyl-1~{H}-indol-3-yl)-N,N-dimethyl-ethanamine
分子 | 名称: 2-(5-chloranyl-2-methyl-1~{H}-indol-3-yl)-N,N-dimethyl-ethanamine タイプ: ligand / ID: 6 / コピー数: 1 / 式: UQL |
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分子量 | 理論値: 236.74 Da |
Chemical component information | ChemComp-UQL: |
-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
緩衝液 | pH: 7.4 |
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凍結 | 凍結剤: ETHANE |
-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 K3 (6k x 4k) / 平均電子線量: 60.0 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: FLOOD BEAM / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2.5 µm / 最小 デフォーカス(公称値): 1.0 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
初期モデル | モデルのタイプ: PDB ENTRY PDBモデル - PDB ID: |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.09 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 286776 |
初期 角度割当 | タイプ: ANGULAR RECONSTITUTION |
最終 角度割当 | タイプ: ANGULAR RECONSTITUTION |