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データを開く
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基本情報
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| タイトル | Cryo-EM structure of the DSO-5a-bound human BRS3-Gq complex | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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試料 |
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キーワード | DSO-5a / MEMBRANE PROTEIN | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 機能・相同性 | 機能・相同性情報bombesin receptor activity / Oplophorus-luciferin 2-monooxygenase / Oplophorus-luciferin 2-monooxygenase activity / negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway / adult feeding behavior / neuropeptide receptor activity / negative regulation of calcium ion-dependent exocytosis / G protein-coupled adenosine receptor signaling pathway / negative regulation of adenylate cyclase activity / G-protein activation ...bombesin receptor activity / Oplophorus-luciferin 2-monooxygenase / Oplophorus-luciferin 2-monooxygenase activity / negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway / adult feeding behavior / neuropeptide receptor activity / negative regulation of calcium ion-dependent exocytosis / G protein-coupled adenosine receptor signaling pathway / negative regulation of adenylate cyclase activity / 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 / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Ca2+ pathway / G alpha (z) signalling events / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / positive regulation of neural precursor cell proliferation / Vasopressin regulates renal water homeostasis via Aquaporins / negative regulation of synaptic transmission / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / positive regulation of urine volume / G alpha (i) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G alpha (12/13) signalling events / Glucagon-type ligand receptors / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Adrenaline,noradrenaline inhibits insulin secretion / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Ca2+ pathway / G alpha (z) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / Extra-nuclear estrogen signaling / G alpha (s) signalling events / G alpha (q) signalling events / photoreceptor outer segment membrane / spectrin binding / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / Vasopressin regulates renal water homeostasis via Aquaporins / gamma-aminobutyric acid signaling pathway / regulation of calcium ion transport / alkylglycerophosphoethanolamine phosphodiesterase activity / adenylate cyclase-activating G protein-coupled bile acid receptor signaling pathway / adenylate cyclase-activating serotonin receptor signaling pathway / regulation of skeletal muscle contraction / negative regulation of apoptotic signaling pathway / PKA activation in glucagon signalling / hair follicle placode formation / developmental growth / intracellular transport / photoreceptor outer segment / D1 dopamine receptor binding / neuronal dense core vesicle / vascular endothelial cell response to laminar fluid shear stress / renal water homeostasis / activation of adenylate cyclase activity / Hedgehog 'off' state / positive regulation of vascular associated smooth muscle cell proliferation / cellular response to acidic pH / adenylate cyclase-activating adrenergic receptor signaling pathway / positive regulation of superoxide anion generation / cardiac muscle cell apoptotic process / Adenylate cyclase inhibitory pathway / photoreceptor inner segment / response to nutrient / cellular response to glucagon stimulus / intracellular glucose homeostasis / Peptide ligand-binding receptors / bioluminescence / positive regulation of insulin secretion involved in cellular response to glucose stimulus / adenylate cyclase activator activity / hippocampal mossy fiber to CA3 synapse / trans-Golgi network membrane / negative regulation of inflammatory response to antigenic stimulus / Regulation of insulin secretion / response to prostaglandin E / bone development / G protein-coupled receptor binding / platelet aggregation 類似検索 - 分子機能 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 生物種 | Homo sapiens (ヒト) / Oplophorus gracilirostris (節足動物) / ![]() ![]() ![]() ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.83 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
データ登録者 | Li J / Li C / Zhou Q / Han W / Fang M / Xu Y / Mai Y / Cui J / Xu H / Zhang Y ...Li J / Li C / Zhou Q / Han W / Fang M / Xu Y / Mai Y / Cui J / Xu H / Zhang Y / Yin W / Wang M | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 資金援助 | 中国, 17件
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引用 | ジャーナル: Acta Pharm Sin B / 年: 2025タイトル: Divergent activation patterns of BRS3 revealed by two Chinese herb-derived agonists. 著者: Jie Li / Changyao Li / Qingtong Zhou / Wei Han / Mingzhu Fang / Youwei Xu / Yiting Mai / Yao Zhang / Jiahua Cui / H Eric Xu / Yan Zhang / Wanchao Yin / Ming-Wei Wang / ![]() 要旨: Bombesin receptor subtype-3 (BRS3) is an orphan G protein-coupled receptor (GPCR) that plays critical roles in energy homeostasis, glucose metabolism, and insulin secretion. Recent structural studies ...Bombesin receptor subtype-3 (BRS3) is an orphan G protein-coupled receptor (GPCR) that plays critical roles in energy homeostasis, glucose metabolism, and insulin secretion. Recent structural studies have elucidated BRS3 signaling mechanisms using synthetic ligands, including BA1 and MK-5046. However, the molecular basis of BRS3 activation by bioactive natural compounds and their derivatives, particularly those derived from traditional Chinese medicine, remains unclear. Here, we present high-resolution cryogenic electron microscopy (cryo-EM) structures of the human BRS3-G complex in both unliganded and active states bound by two herb-derived compounds (DSO-5a and oridonin), at resolutions of 2.9, 2.8, and 2.9 Å, respectively. These structures display distinct ligand recognition patterns between DSO-5a and oridonin. Although both compounds bind to the orthosteric pocket, they differentially engage the interaction network of BRS3, as demonstrated by mutagenesis studies assessing calcium mobilization and inositol phosphate 1 (IP1) accumulation. These findings enhance our understanding of BRS3 activation and provide valuable insights into the development of small-molecule BRS3 modulators with therapeutic potential. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 履歴 |
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構造の表示
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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_61941.map.gz | 59.6 MB | EMDBマップデータ形式 | |
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| ヘッダ (付随情報) | emd-61941-v30.xml emd-61941.xml | 26.4 KB 26.4 KB | 表示 表示 | EMDBヘッダ |
| FSC (解像度算出) | emd_61941_fsc.xml | 8.4 KB | 表示 | FSCデータファイル |
| 画像 | emd_61941.png | 110.4 KB | ||
| Filedesc metadata | emd-61941.cif.gz | 7.6 KB | ||
| その他 | emd_61941_half_map_1.map.gz emd_61941_half_map_2.map.gz | 59.3 MB 59.3 MB | ||
| アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-61941 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-61941 | HTTPS FTP |
-関連構造データ
| 関連構造データ | ![]() 9k07MC ![]() 9lwpC 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 F&H 検索 |
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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 |
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マップ
| ファイル | ダウンロード / ファイル: emd_61941.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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| 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: 1.071 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
-ハーフマップ: #2
| ファイル | emd_61941_half_map_1.map | ||||||||||||
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| 投影像・断面図 |
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| 密度ヒストグラム |
-ハーフマップ: #1
| ファイル | emd_61941_half_map_2.map | ||||||||||||
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| 投影像・断面図 |
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試料の構成要素
-全体 : Cryo-EM structure of the DSO-5a-bound human BRS3-miniGq complex
| 全体 | 名称: Cryo-EM structure of the DSO-5a-bound human BRS3-miniGq complex |
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| 要素 |
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-超分子 #1: Cryo-EM structure of the DSO-5a-bound human BRS3-miniGq complex
| 超分子 | 名称: Cryo-EM structure of the DSO-5a-bound human BRS3-miniGq complex タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#6 |
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| 由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Bombesin receptor subtype-3,Oplophorus-luciferin 2-monooxygenase ...
| 分子 | 名称: Bombesin receptor subtype-3,Oplophorus-luciferin 2-monooxygenase catalytic subunit タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO / EC番号: Oplophorus-luciferin 2-monooxygenase |
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| 由来(天然) | 生物種: Oplophorus gracilirostris (節足動物) |
| 分子量 | 理論値: 67.457555 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MKTIIALSYI FCLVFAMAQR QPHSPNQTLI SITNDTESSS SVVSNDNTNK GWSGDNSPGI EALCAIYITY AVIISVGILG NAILIKVFF KTKSMQTVPN IFITSLAFGD LLLLLTCVPV DATHYLAEGW LFGRIGCKVL SFIRLTSVGV SVFTLTILSA D RYKAVVKP ...文字列: MKTIIALSYI FCLVFAMAQR QPHSPNQTLI SITNDTESSS SVVSNDNTNK GWSGDNSPGI EALCAIYITY AVIISVGILG NAILIKVFF KTKSMQTVPN IFITSLAFGD LLLLLTCVPV DATHYLAEGW LFGRIGCKVL SFIRLTSVGV SVFTLTILSA D RYKAVVKP LERQPSNAIL KTCVKAGCVW IVSMIFALPE AIFSNVYTFR DPNKNMTFES CTSYPVSKKL LQEIHSLLCF LV FYIIPLS IISVYYSLIA RTLYKSTLNI PTEEQSHARK QIESRKRIAR TVLVLVALFA LCWLPNHLLY LYHSFTSQTY VDP SAMHFI FTIFSRVLAF SNSCVNPFAL YWLSKSFQKH FKAQLFCCKA ERPEPPVADT SLTTLAVMGT VPGTGSIQMS EISV TSFTG CSVKQAEDRF GSSGGGGSGG GGSSGVFTLE DFVGDWEQTA AYNLDQVLEQ GGVSSLLQNL AVSVTPIQRI VRSGE NALK IDIHVIIPYE GLSADQMAQI EEVFKVVYPV DDHHFKVILP YGTLVIDGVT PNMLNYFGRP YEGIAVFDGK KITVTG TLW NGNKIIDERL ITPDGSMLFR VTINSGGSEN LYFQGGSAGS AHHHHHHHH UniProtKB: Bombesin receptor subtype-3, Oplophorus-luciferin 2-monooxygenase catalytic subunit |
-分子 #2: Guanine nucleotide-binding protein G(i) subunit alpha-2,Guanine n...
| 分子 | 名称: Guanine nucleotide-binding protein G(i) subunit alpha-2,Guanine nucleotide-binding protein G(s) subunit alpha isoforms short タイプ: protein_or_peptide / ID: 2 / 詳細: Gi2-mini-Gq chimeric,Gi2-mini-Gq chimeric / コピー数: 1 / 光学異性体: LEVO EC番号: 加水分解酵素; 酸無水物に作用; GTPに作用・細胞または細胞小器官の運動に関与 |
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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: ![]() |
| 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 UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-2, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(s) subunit alpha ...UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-2, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short |
-分子 #3: scFv16
| 分子 | 名称: scFv16 / 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: 28.668922 KDa |
| 組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
| 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 #4: 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: 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: 37.915496 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 WDSFLKIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-分子 #5: 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: 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: 7.729947 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: ASNNTASIAQ ARKLVEQLKM EANIDRIKVS KAAADLMAYC EAHAKEDPLL TPVPASENPF REKKFFCAIL UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-分子 #6: Nanobody-35
| 分子 | 名称: Nanobody-35 / タイプ: protein_or_peptide / ID: 6 / 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: 15.343019 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MAQVQLQESG GGLVQPGGSL RLSCAASGFT FSNYKMNWVR QAPGKGLEWV SDISQSGASI SYTGSVKGRF TISRDNAKNT LYLQMNSLK PEDTAVYYCA RCPAPFTRDC FDVTSTTYAY RGQGTQVTVS SHHHHHHEPE A |
-分子 #7: [(1~{S})-1-[1,4-dimethoxy-8-nitroso-5-(oxidanylamino)naphthalen-2...
| 分子 | 名称: [(1~{S})-1-[1,4-dimethoxy-8-nitroso-5-(oxidanylamino)naphthalen-2-yl]-2,2-dimethyl-but-3-enyl] furan-2-carboxylate タイプ: ligand / ID: 7 / コピー数: 1 / 式: A1EL6 |
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| 分子量 | 理論値: 440.446 Da |
-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 |
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試料調製
| 緩衝液 | pH: 7.5 |
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| 凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
| 顕微鏡 | FEI TECNAI 10 |
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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: 80.0 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: 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): 1.5 µm |
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コントローラー
万見について




キーワード
Homo sapiens (ヒト)
Oplophorus gracilirostris (節足動物)
データ登録者
中国, 17件
引用






























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Y (Row.)
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解析
