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基本情報
登録情報 | ![]() | |||||||||
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タイトル | Serotonin 5A (5-HT5A) receptor-Gi protein complex | |||||||||
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機能・相同性 | ![]() adenylate cyclase-inhibiting serotonin receptor signaling pathway / Serotonin receptors / serotonin binding / G protein-coupled serotonin receptor activity / postsynaptic specialization membrane / neurotransmitter receptor activity / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling ...adenylate cyclase-inhibiting serotonin receptor signaling pathway / Serotonin receptors / serotonin binding / G protein-coupled serotonin receptor activity / postsynaptic specialization membrane / neurotransmitter receptor activity / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / regulation of mitotic spindle organization / cellular response to forskolin / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Regulation of insulin secretion / G protein-coupled receptor binding / hippocampus development / electron transport chain / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / adenylate cyclase-activating G protein-coupled receptor signaling pathway / 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 / response to peptide hormone / 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 / 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 / GDP binding / 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 / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / response to estradiol / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / cell cortex / midbody / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / chemical synaptic transmission / perikaryon / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / periplasmic space / electron transfer activity / iron ion binding / G protein-coupled receptor signaling pathway / cell cycle / cell division / lysosomal membrane / GTPase activity / centrosome / synapse / dendrite / heme binding / protein-containing complex binding / nucleolus / GTP binding / magnesium ion binding / signal transduction / extracellular exosome / nucleoplasm / membrane / plasma membrane / cytoplasm 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: 3.1 Å | |||||||||
![]() | Tan Y / Xu P / Huang S / Xu HE / Jiang Y | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural insights into the ligand binding and G coupling of serotonin receptor 5-HT. 著者: Yangxia Tan / Peiyu Xu / Sijie Huang / Gong Yang / Fulai Zhou / Xinheng He / Honglei Ma / H Eric Xu / Yi Jiang / ![]() 要旨: 5-hydroxytryptamine receptor 5A (5-HT) belongs to the 5-HT receptor family and signals through the G protein. It is involved in nervous system regulation and an attractive target for the treatment of ...5-hydroxytryptamine receptor 5A (5-HT) belongs to the 5-HT receptor family and signals through the G protein. It is involved in nervous system regulation and an attractive target for the treatment of psychosis, depression, schizophrenia, and neuropathic pain. 5-HT is the only G-coupled 5-HT receptor subtype lacking a high-resolution structure, which hampers the mechanistic understanding of ligand binding and G coupling for 5-HT. Here we report a cryo-electron microscopy structure of the 5-HT-G complex bound to 5-Carboxamidotryptamine (5-CT). Combined with functional analysis, this structure reveals the 5-CT recognition mechanism and identifies the receptor residue at 6.55 as a determinant of the 5-CT selectivity for G-coupled 5-HT receptors. In addition, 5-HT shows an overall conserved G protein coupling mode compared with other G-coupled 5-HT receptors. These findings provide comprehensive insights into the ligand binding and G protein coupling of G-coupled 5-HT receptors and offer a template for the design of 5-HT-selective drugs. | |||||||||
履歴 |
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構造の表示
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マップデータ | ![]() | 28.7 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 16.5 KB 16.5 KB | 表示 表示 | ![]() |
画像 | ![]() | 78.4 KB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 418.6 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 418.2 KB | 表示 | |
XML形式データ | ![]() | 5.9 KB | 表示 | |
CIF形式データ | ![]() | 6.7 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 7x5hMC 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 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 1.071 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
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試料の構成要素
-全体 : 5-HT5A-Gi-scFv16 complex
全体 | 名称: 5-HT5A-Gi-scFv16 complex |
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要素 |
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-超分子 #1: 5-HT5A-Gi-scFv16 complex
超分子 | 名称: 5-HT5A-Gi-scFv16 complex / タイプ: complex / キメラ: Yes / 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: ![]() |
-超分子 #2: 5-HT5A-Gi
超分子 | 名称: 5-HT5A-Gi / タイプ: complex / キメラ: Yes / ID: 2 / 親要素: 1 / 含まれる分子: #1-#3, #5 |
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由来(天然) | 生物種: ![]() ![]() |
組換発現 | 生物種: ![]() |
-超分子 #3: scFv16
超分子 | 名称: scFv16 / タイプ: complex / キメラ: Yes / ID: 3 / 親要素: 1 / 含まれる分子: #4 |
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-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: 40.414047 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKNTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKNTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTTGIVETH FTFKDLHFKM FDVGAQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHASM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY PEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCS 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: ![]() |
分子量 | 理論値: 40.226992 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MGSLLQSELD QLRQEAEQLK NQIRDARKAC ADATLSQITN NIDPVGRIQM RTRRTLRGHL AKIYAMHWGT DSRLLVSASQ DGKLIIWDS YTTNKVHAIP LRSSWVMTCA YAPSGNYVAC GGLDNICSIY NLKTREGNVR VSRELAGHTG YLSCCRFLDD N QIVTSSGD ...文字列: MGSLLQSELD QLRQEAEQLK NQIRDARKAC ADATLSQITN NIDPVGRIQM RTRRTLRGHL AKIYAMHWGT DSRLLVSASQ DGKLIIWDS YTTNKVHAIP LRSSWVMTCA YAPSGNYVAC GGLDNICSIY NLKTREGNVR VSRELAGHTG YLSCCRFLDD N QIVTSSGD TTCALWDIET GQQTTTFTGH TGDVMSLSLA PDTRLFVSGA CDASAKLWDV REGMCRQTFT GHESDINAIC FF PNGNAFA TGSDDATCRL FDLRADQELM TYSHDNIICG ITSVSFSKSG RLLLAGYDDF NCNVWDALKA DRAGVLAGHD NRV SCLGVT DDGMAVATGS WDSFLKIWNG SSGGGGSGGG GSSGVSGWRL FKKIS |
-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: 7.729947 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: ASNNTASIAQ ARKLVEQLKM EANIDRIKVS KAAADLMAYC EAHAKEDPLL TPVPASENPF REKKFFCAIL |
-分子 #4: scFv16
分子 | 名称: scFv16 / 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: ![]() ![]() |
分子量 | 理論値: 30.552234 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 GAGTKLELK |
-分子 #5: Soluble cytochrome b562,5-hydroxytryptamine receptor 5A,hydroxytr...
分子 | 名称: Soluble cytochrome b562,5-hydroxytryptamine receptor 5A,hydroxytryptamine receptor 5A 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: 77.127281 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MKTIIALSYI FCLVFADYKD DDDAKLQTMH HHHHHHHHHH HHHHADLEDN WETLNDNLKV IEKADNAAQV KDALTKMRAA ALDAQKATP PKLEDKSPDS PEMKDFRHGF DILVGQIDDA LKLANEGKVK EAQAAAEQLK TTRNAYIQKY LASENLYFQG G TDLPVNLT ...文字列: MKTIIALSYI FCLVFADYKD DDDAKLQTMH HHHHHHHHHH HHHHADLEDN WETLNDNLKV IEKADNAAQV KDALTKMRAA ALDAQKATP PKLEDKSPDS PEMKDFRHGF DILVGQIDDA LKLANEGKVK EAQAAAEQLK TTRNAYIQKY LASENLYFQG G TDLPVNLT SFSLSTPSPL ETNHSLGKDD LRPSSPLLSV FGVLILTLLG FLVAATFAWN LLVLATILRV RTFHRVPHNL VA SMAVSDV LVAALVMPLS LVHELSGRRW QLGRRLCQLW IACDVLCCTA SIWNVTAIAL DRYWSITRHM EYTLRTRKCV SNV MIALTW ALSAVISLAP LLFGWGETYS EGSEECQVSR EPSYAVFSTV GAFYLPLCVV LFVYWKIYKA AKFRVGSRKT NSVS PISEA VEVKDSAKQP QMVFTVRHAT VTFQPEGDTW REQKEQRAAL MVGILIGVFV LCWIPFFLTE LISPLCSCDI PAIWK SIFL WLGYSNSFFN PLIYTAFNKN YNSAFKNFFS RQHGSSGGGG SGGGGSSGVF TLEDFVGDWE QTAAYNLDQV LEQGGV SSL LQNLAVSVTP IQRIVRSGEN ALKIDIHVII PYEGLSADQM AQIEEVFKVV YPVDDHHFKV ILPYGTLVID GVTPNML NY FGRPYEGIAV FDGKKITVTG TLWNGNKIID ERLITPDGSM LFRVTINS |
-分子 #6: 3-(2-azanylethyl)-1H-indole-5-carboxamide
分子 | 名称: 3-(2-azanylethyl)-1H-indole-5-carboxamide / タイプ: ligand / ID: 6 / コピー数: 1 / 式: 8K3 |
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分子量 | 理論値: 203.24 Da |
Chemical component information | ![]() ChemComp-8K3: |
-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 | particle |
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試料調製
緩衝液 | pH: 7.4 |
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凍結 | 凍結剤: ETHANE-PROPANE |
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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 K3 (6k x 4k) / 平均電子線量: 70.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: OTHER |
電子光学系 | 照射モード: OTHER / 撮影モード: OTHER / 最大 デフォーカス(公称値): 2.2 µm / 最小 デフォーカス(公称値): 1.2 µm |
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: EMDB MAP EMDB ID: |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.1 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 754854 |
初期 角度割当 | タイプ: RANDOM ASSIGNMENT |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |