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データを開く
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基本情報
| 登録情報 | ![]() | |||||||||
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| タイトル | CryoEM structure of Go-coupled NTSR1 with a biased allosteric modulator | |||||||||
マップデータ | Go-coupled NTSR1 with a biased allosteric modulator | |||||||||
試料 |
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キーワード | GPCR / neurotensin receptor / allosterism / SBI-553 / MEMBRANE PROTEIN | |||||||||
| 機能・相同性 | 機能・相同性情報regulation of locomotion involved in locomotory behavior / Peptide ligand-binding receptors / neuropeptide receptor binding / G protein-coupled neurotensin receptor activity / inositol phosphate catabolic process / symmetric synapse / positive regulation of locomotion / regulation of inositol trisphosphate biosynthetic process / positive regulation of gamma-aminobutyric acid secretion / D-aspartate import across plasma membrane ...regulation of locomotion involved in locomotory behavior / Peptide ligand-binding receptors / neuropeptide receptor binding / G protein-coupled neurotensin receptor activity / inositol phosphate catabolic process / symmetric synapse / positive regulation of locomotion / regulation of inositol trisphosphate biosynthetic process / positive regulation of gamma-aminobutyric acid secretion / D-aspartate import across plasma membrane / response to antipsychotic drug / positive regulation of arachidonate secretion / neuron spine / L-glutamate import across plasma membrane / vocalization behavior / neuropeptide hormone activity / regulation of behavioral fear response / regulation of respiratory gaseous exchange / cAMP biosynthetic process / positive regulation of inhibitory postsynaptic potential / negative regulation of systemic arterial blood pressure / negative regulation of release of sequestered calcium ion into cytosol / G alpha (q) signalling events / hyperosmotic response / digestive tract development / positive regulation of glutamate secretion / response to mineralocorticoid / cellular response to lithium ion / response to food / regulation of membrane depolarization / response to lipid / response to corticosterone / temperature homeostasis / positive regulation of inositol phosphate biosynthetic process / detection of temperature stimulus involved in sensory perception of pain / response to stress / associative learning / cellular response to dexamethasone stimulus / conditioned place preference / response to axon injury / transport vesicle / axon terminus / blood vessel diameter maintenance / positive regulation of release of sequestered calcium ion into cytosol / dendritic shaft / response to amphetamine / learning / adult locomotory behavior / response to cocaine / neuropeptide signaling pathway / liver development / cellular response to nerve growth factor stimulus / visual learning / cytoplasmic side of plasma membrane / Olfactory Signaling Pathway / Activation of the phototransduction cascade / terminal bouton / G protein-coupled acetylcholine receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / response to estradiol / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / ADORA2B mediated anti-inflammatory cytokines production / G beta:gamma signalling through PI3Kgamma / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / cellular response to prostaglandin E stimulus / heterotrimeric G-protein complex / G-protein beta-subunit binding / G alpha (12/13) signalling events / Inactivation, recovery and regulation of the phototransduction cascade / extracellular vesicle / sensory perception of taste / Thrombin signalling through proteinase activated receptors (PARs) / signaling receptor complex adaptor activity / retina development in camera-type eye / GTPase binding / fibroblast proliferation / Ca2+ pathway / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / G alpha (i) signalling events 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: 2.89 Å | |||||||||
データ登録者 | Krumm BE / DiBerto JF / Olsen RHJ / Kang H / Slocum ST / Zhang S / Strachan RT / Fay JF / Roth BL | |||||||||
| 資金援助 | 米国, 1件
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引用 | ジャーナル: Biochemistry / 年: 2023タイトル: Neurotensin Receptor Allosterism Revealed in Complex with a Biased Allosteric Modulator. 著者: Brian E Krumm / Jeffrey F DiBerto / Reid H J Olsen / Hye Jin Kang / Samuel T Slocum / Shicheng Zhang / Ryan T Strachan / Xi-Ping Huang / Lauren M Slosky / Anthony B Pinkerton / Lawrence S ...著者: Brian E Krumm / Jeffrey F DiBerto / Reid H J Olsen / Hye Jin Kang / Samuel T Slocum / Shicheng Zhang / Ryan T Strachan / Xi-Ping Huang / Lauren M Slosky / Anthony B Pinkerton / Lawrence S Barak / Marc G Caron / Terry Kenakin / Jonathan F Fay / Bryan L Roth / ![]() 要旨: The NTSR1 neurotensin receptor (NTSR1) is a G protein-coupled receptor (GPCR) found in the brain and peripheral tissues with neurotensin (NTS) being its endogenous peptide ligand. In the brain, NTS ...The NTSR1 neurotensin receptor (NTSR1) is a G protein-coupled receptor (GPCR) found in the brain and peripheral tissues with neurotensin (NTS) being its endogenous peptide ligand. In the brain, NTS modulates dopamine neuronal activity, induces opioid-independent analgesia, and regulates food intake. Recent studies indicate that biasing NTSR1 toward β-arrestin signaling can attenuate the actions of psychostimulants and other drugs of abuse. Here, we provide the cryoEM structures of NTSR1 ternary complexes with heterotrimeric Gq and GoA with and without the brain-penetrant small-molecule SBI-553. In functional studies, we discovered that SBI-553 displays complex allosteric actions exemplified by negative allosteric modulation for G proteins that are Gα subunit selective and positive allosteric modulation and agonism for β-arrestin translocation at NTSR1. Detailed structural analysis of the allosteric binding site illuminated the structural determinants for biased allosteric modulation of SBI-553 on NTSR1. | |||||||||
| 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_29302.map.gz | 55.1 MB | EMDBマップデータ形式 | |
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| ヘッダ (付随情報) | emd-29302-v30.xml emd-29302.xml | 20.9 KB 20.9 KB | 表示 表示 | EMDBヘッダ |
| 画像 | emd_29302.png | 69.3 KB | ||
| Filedesc metadata | emd-29302.cif.gz | 6.8 KB | ||
| その他 | emd_29302_half_map_1.map.gz emd_29302_half_map_2.map.gz | 59.4 MB 59.4 MB | ||
| アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-29302 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-29302 | HTTPS FTP |
-関連構造データ
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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_29302.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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| 注釈 | Go-coupled NTSR1 with a biased allosteric modulator | ||||||||||||||||||||||||||||||||||||
| 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: 0.88 Å | ||||||||||||||||||||||||||||||||||||
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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: Half Map 1
| ファイル | emd_29302_half_map_1.map | ||||||||||||
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| 注釈 | Half Map 1 | ||||||||||||
| 投影像・断面図 |
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| 密度ヒストグラム |
-ハーフマップ: Half Map 2
| ファイル | emd_29302_half_map_2.map | ||||||||||||
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| 注釈 | Half Map 2 | ||||||||||||
| 投影像・断面図 |
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| 密度ヒストグラム |
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試料の構成要素
-全体 : Ternary complex of NTSR1 MiniGo heterotrimer with scFv16
| 全体 | 名称: Ternary complex of NTSR1 MiniGo heterotrimer with scFv16 |
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| 要素 |
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-超分子 #1: Ternary complex of NTSR1 MiniGo heterotrimer with scFv16
| 超分子 | 名称: Ternary complex of NTSR1 MiniGo heterotrimer with scFv16 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: ![]() |
| 分子量 | 理論値: 147 KDa |
-分子 #1: Neurotensin receptor type 1
| 分子 | 名称: Neurotensin receptor type 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: 45.939211 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MHHHHHHHHH HSDLEVLFQG PLGSGAPTSE SDTAGPNSDL DVNTDIYSKV LVTAIYLALF VVGTVGNSVT LFTLARKKSL QSLQSTVHY HLGSLALSDL LILLLAMPVE LYNFIWVHHP WAFGDAGCRG YYFLRDACTY ATALNVASLS VERYLAICHP F KAKTLMSR ...文字列: MHHHHHHHHH HSDLEVLFQG PLGSGAPTSE SDTAGPNSDL DVNTDIYSKV LVTAIYLALF VVGTVGNSVT LFTLARKKSL QSLQSTVHY HLGSLALSDL LILLLAMPVE LYNFIWVHHP WAFGDAGCRG YYFLRDACTY ATALNVASLS VERYLAICHP F KAKTLMSR SRTKKFISAI WLASALLAIP MLFTMGLQNR SADGTHPGGL VCTPIVDTAT VKVVIQVNTF MSFLFPMLVI SI LNTVIAN KLTVMVHQAA EQGRVCTVGT HNGLEHSTFN MTIEPGRVQA LRHGVLVLRA VVIAFVVCWL PYHVRRLMFC YIS DEQWTT FLFDFYHYFY MLTNALFYAS SAINPILYNL VSANFRQVFL STLACLCPGW RHRRKKRPTF SRKPNSMSSN HAFS TSATR ETLY UniProtKB: Neurotensin receptor type 1 |
-分子 #2: Neurotensin/neuromedin N
| 分子 | 名称: Neurotensin/neuromedin N / 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: 819.007 Da |
| 配列 | 文字列: RRPYIL UniProtKB: Neurotensin/neuromedin N |
-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: ![]() |
| 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 UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-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: ![]() |
| 配列 | 文字列: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-分子 #5: MiniGo
| 分子 | 名称: MiniGo / 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: 25.451166 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MGCTLSAEDK AAVERSKMIE KNLKEDGISA AKDVKLLLLG ADNSGKSTIV KQMKIIHGGS GGSGGTTGIV ETHFTFKNLH FRLFDVGGQ RSERKKWIHC FEDVTAIIFC VDLSDYNRMH ESLMLFDSIC NNKFFIDTSI ILFLNKKDLF GEKIKKSPLT I CFPEYTGP ...文字列: MGCTLSAEDK AAVERSKMIE KNLKEDGISA AKDVKLLLLG ADNSGKSTIV KQMKIIHGGS GGSGGTTGIV ETHFTFKNLH FRLFDVGGQ RSERKKWIHC FEDVTAIIFC VDLSDYNRMH ESLMLFDSIC NNKFFIDTSI ILFLNKKDLF GEKIKKSPLT I CFPEYTGP NTYEDAAAYI QAQFESKNRS PNKEIYCHMT CATDTNNAQV IFDAVTDIII ANNLRGCGLY |
-分子 #6: scFv16
| 分子 | 名称: scFv16 / 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: 28.668922 KDa |
| 組換発現 | 生物種: ![]() |
| 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 #7: 2-[{2-(1-fluorocyclopropyl)-4-[4-(2-methoxyphenyl)piperidin-1-yl]...
| 分子 | 名称: 2-[{2-(1-fluorocyclopropyl)-4-[4-(2-methoxyphenyl)piperidin-1-yl]quinazolin-6-yl}(methyl)amino]ethan-1-ol タイプ: ligand / ID: 7 / コピー数: 1 / 式: SRW |
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| 分子量 | 理論値: 450.548 Da |
| Chemical component information | ![]() ChemComp-SRW: |
-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 / 詳細: 20mM Hepes, 0.1M NaCl, 0.00075% LMNG, 0.00075% GDN |
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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 TALOS ARCTICA |
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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: 44.0 e/Å2 |
| 電子線 | 加速電圧: 200 kV / 電子線源: FIELD EMISSION GUN |
| 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): 3.2 µm / 最小 デフォーカス(公称値): 0.1 µm |
| 実験機器 | ![]() モデル: Talos Arctica / 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: 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: 2.89 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 461511 |
| 初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
| 最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
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万見について




キーワード
Homo sapiens (ヒト)
データ登録者
米国, 1件
引用

























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FIELD EMISSION GUN

