+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-31982 | |||||||||
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タイトル | MT2-remalteon-Gi complex | |||||||||
マップデータ | ||||||||||
試料 |
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機能・相同性 | 機能・相同性情報 positive regulation of circadian sleep/wake cycle, non-REM sleep / melatonin receptor activity / regulation of neuronal action potential / negative regulation of transmission of nerve impulse / positive regulation of transmission of nerve impulse / Class A/1 (Rhodopsin-like receptors) / G-protein activation / Activation of the phototransduction cascade / : / Glucagon-type ligand receptors ...positive regulation of circadian sleep/wake cycle, non-REM sleep / melatonin receptor activity / regulation of neuronal action potential / negative regulation of transmission of nerve impulse / positive regulation of transmission of nerve impulse / Class A/1 (Rhodopsin-like receptors) / G-protein activation / Activation of the phototransduction cascade / : / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Ca2+ pathway / Activation of G protein gated Potassium channels / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G alpha (z) signalling events / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / camera-type eye development / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / G alpha (i) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / alkylglycerophosphoethanolamine phosphodiesterase activity / photoreceptor outer segment membrane / negative regulation of vasoconstriction / spectrin binding / negative regulation of cGMP-mediated signaling / negative regulation of cytosolic calcium ion concentration / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / regulation of insulin secretion / photoreceptor outer segment / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / negative regulation of insulin secretion / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / regulation of mitotic spindle organization / cellular response to forskolin / cardiac muscle cell apoptotic process / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / photoreceptor inner segment / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / G-protein beta/gamma-subunit complex binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / ADP signalling through P2Y purinoceptor 12 / response to peptide hormone / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (z) signalling events / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / GPER1 signaling / GDP binding / heterotrimeric G-protein complex / signaling receptor complex adaptor activity / glucose homeostasis / retina development in camera-type eye / GTPase binding / cell body / phospholipase C-activating G protein-coupled receptor signaling pathway / 細胞皮質 / midbody / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / cellular response to hypoxia / chemical synaptic transmission / G alpha (s) signalling events / negative regulation of neuron apoptotic process / cell population proliferation / Extra-nuclear estrogen signaling / 細胞周期 / G protein-coupled receptor signaling pathway / 細胞分裂 / lysosomal membrane / GTPase activity / 中心体 / 樹状突起 / シナプス / protein-containing complex binding / GTP binding / 核小体 / magnesium ion binding / extracellular exosome / 核質 / 細胞膜 / 細胞質 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / Rattus norvegicus (ドブネズミ) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.46 Å | |||||||||
データ登録者 | Wang QG / Lu QY | |||||||||
資金援助 | 中国, 1件
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引用 | ジャーナル: Nat Commun / 年: 2022 タイトル: Structural basis of the ligand binding and signaling mechanism of melatonin receptors. 著者: Qinggong Wang / Qiuyuan Lu / Qiong Guo / Maikun Teng / Qingguo Gong / Xu Li / Yang Du / Zheng Liu / Yuyong Tao / 要旨: Melatonin receptors (MT and MT in humans) are family A G protein-coupled receptors that respond to the neurohormone melatonin to regulate circadian rhythm and sleep. Numerous efforts have been made ...Melatonin receptors (MT and MT in humans) are family A G protein-coupled receptors that respond to the neurohormone melatonin to regulate circadian rhythm and sleep. Numerous efforts have been made to develop drugs targeting melatonin receptors for the treatment of insomnia, circadian rhythm disorder, and cancer. However, designing subtype-selective melatonergic drugs remains challenging. Here, we report the cryo-EM structures of the MT-G signaling complex with 2-iodomelatonin and ramelteon and the MT-G signaling complex with ramelteon. These structures, together with the reported functional data, reveal that although MT and MT possess highly similar orthosteric ligand-binding pockets, they also display distinctive features that could be targeted to design subtype-selective drugs. The unique structural motifs in MT and MT mediate structural rearrangements with a particularly wide opening on the cytoplasmic side. G is engaged in the receptor core shared by MT and MT and presents a conformation deviating from those in other G complexes. Together, our results provide new clues for designing melatonergic drugs and further insights into understanding the G protein coupling mechanism. | |||||||||
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_31982.map.gz | 33 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-31982-v30.xml emd-31982.xml | 13.7 KB 13.7 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_31982.png | 43.8 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-31982 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-31982 | 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_31982.map.gz / 形式: CCP4 / 大きさ: 64 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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:
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 : melatonin receptor 2 with G peotein complex
全体 | 名称: melatonin receptor 2 with G peotein complex |
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要素 |
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-超分子 #1: melatonin receptor 2 with G peotein complex
超分子 | 名称: melatonin receptor 2 with G peotein complex / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#4 |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Melatonin receptor type 1B
分子 | 名称: Melatonin receptor type 1B / 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: 40.308285 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MSENGSFANC CEAGGWAVRP GWSGAGSARP SRTPRPPWVA PALSAVLIVT TAVDVVGNLL VILSVLRNRK LRNAGNLFLV SLALADLVV AFYPYPLILV AIFYDGWAFG EEHCKASAFV MGLSVIGSVW NITAIAINRY LYICHSMAYH RIYRRWHTPL H ICLIWLLT ...文字列: MSENGSFANC CEAGGWAVRP GWSGAGSARP SRTPRPPWVA PALSAVLIVT TAVDVVGNLL VILSVLRNRK LRNAGNLFLV SLALADLVV AFYPYPLILV AIFYDGWAFG EEHCKASAFV MGLSVIGSVW NITAIAINRY LYICHSMAYH RIYRRWHTPL H ICLIWLLT VVALLPNFFV GSLEYDPRIY SCTFIQTAST QYTAAVVVIH FLLPIAVVSF CYLRIWVLVL QARRKAKPES RL CLKPSDL RSFLTMFVVF VIFAICWAPL NCIGLAVAIN PQEMAPQIPE GLFVTSYLLA YFNSCLNAIV YGLLNQNFRR EYK RILLAL WNPRHCIQDA SKGSHAEGLQ SPAPPIIGVQ HQADAL |
-分子 #2: 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: 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: 40.340887 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: GGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...文字列: GGCTLSAEDK 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 |
-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: Rattus norvegicus (ドブネズミ) |
分子量 | 理論値: 39.021648 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: HHHHHHHHMG SLLQSELDEL RQEAEQLKNQ IRDARKACAD ATLSQITNNI DPVGRIQMRT RRTLRGHLAK IYAMHWGTDS RLLVSASQD GKLIIWDSYT TNKVHAIPLR SSWVMTCAYA PSGNYVACGG LDNICSIYNL KTRQGNVRVS RELAGHTGYL S CCRFLDDN ...文字列: HHHHHHHHMG SLLQSELDEL RQEAEQLKNQ IRDARKACAD ATLSQITNNI DPVGRIQMRT RRTLRGHLAK IYAMHWGTDS RLLVSASQD GKLIIWDSYT TNKVHAIPLR SSWVMTCAYA PSGNYVACGG LDNICSIYNL KTRQGNVRVS RELAGHTGYL S CCRFLDDN QIVTSSGDTT CALWDIETGQ QTTTFTGHTG DVMSLSLAPD TRLFVSGACD ASAKLWDVRE GMCRQTFTGH ES DINAICF FPDGNAFATG SDDATCRLFD LRADQELMTY SHDNIICGIT SVSFSKSGRL LLAGYDDFNC NVWDALKADR AGV LAGHDN RVSCLGVTDD GMAVATGSWD SFLKIWN |
-分子 #4: scFv16
分子 | 名称: scFv16 / タイプ: protein_or_peptide / ID: 4 / コピー数: 2 / 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: 34.767035 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: ASNNTASIAQ ARKLVQQLKM EANIDRIKVS KAAADLMAYC EAHAKEDPLL TPVPASQNPF REKKFFCDVQ LVESGGGLVQ PGGSRKLSC SASGFAFSSF GMHWVRQAPE KGLEWVAYIS SGSGTIYYAD TVKGRFTISR DDPKNTLFLQ MTSLRSEDTA M YYCVRSIY ...文字列: ASNNTASIAQ ARKLVQQLKM EANIDRIKVS KAAADLMAYC EAHAKEDPLL TPVPASQNPF REKKFFCDVQ LVESGGGLVQ PGGSRKLSC SASGFAFSSF GMHWVRQAPE KGLEWVAYIS SGSGTIYYAD TVKGRFTISR DDPKNTLFLQ MTSLRSEDTA M YYCVRSIY YYGSSPFDFW GQGTTLTVSS GGGGSGGGGS GGGGSDIVMT QATSSVPVTP GESVSISCRS SKSLLHSNGN TY LYWFLQR PGQSPQLLIY RMSNLASGVP ERFSGSGSGT AFTLTISRLE AEDVGVYYCM QHLEYPLTFG AGTKLELKGS LEV LFQ |
-分子 #5: N-{2-[(8S)-1,6,7,8-tetrahydro-2H-indeno[5,4-b]furan-8-yl]ethyl}pr...
分子 | 名称: N-{2-[(8S)-1,6,7,8-tetrahydro-2H-indeno[5,4-b]furan-8-yl]ethyl}propanamide タイプ: ligand / ID: 5 / コピー数: 1 / 式: JEV |
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分子量 | 理論値: 259.343 Da |
Chemical component information | ChemComp-JEV: |
-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 | 2D array |
-試料調製
緩衝液 | pH: 7.4 |
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凍結 | 凍結剤: OTHER |
-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 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELDBright-field microscopy / 最大 デフォーカス(公称値): 2.0 µm / 最小 デフォーカス(公称値): 1.2 µm |
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 |
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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初期 角度割当 | タイプ: ANGULAR RECONSTITUTION |
最終 角度割当 | タイプ: ANGULAR RECONSTITUTION |
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.46 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 335170 |