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基本情報
| 登録情報 | ![]() | |||||||||
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| タイトル | Structure of human class T GPCR TAS2R14-Gi complex with Aristolochic acid A. | |||||||||
マップデータ | ||||||||||
試料 |
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キーワード | GPCR / Tas2R14 / Gi / GOQ / Bitter Receptor. / SIGNALING PROTEIN | |||||||||
| 機能・相同性 | 機能・相同性情報bitter taste receptor activity / taste receptor activity / detection of chemical stimulus involved in sensory perception of bitter taste / ganglioside catabolic process / Class C/3 (Metabotropic glutamate/pheromone receptors) / oligosaccharide catabolic process / exo-alpha-sialidase / exo-alpha-sialidase activity / adenylate cyclase inhibitor activity / positive regulation of protein localization to cell cortex ...bitter taste receptor activity / taste receptor activity / detection of chemical stimulus involved in sensory perception of bitter taste / ganglioside catabolic process / Class C/3 (Metabotropic glutamate/pheromone receptors) / oligosaccharide catabolic process / exo-alpha-sialidase / exo-alpha-sialidase activity / adenylate cyclase inhibitor activity / positive regulation of protein localization to cell cortex / T cell migration / positive regulation of relaxation of smooth muscle / Adenylate cyclase inhibitory pathway / D2 dopamine receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / G protein-coupled serotonin receptor binding / cellular response to forskolin / regulation of mitotic spindle organization / chemokine-mediated signaling pathway / Regulation of insulin secretion / neuropeptide signaling pathway / response to prostaglandin E / positive regulation of cholesterol biosynthetic process / negative regulation of insulin secretion / G protein-coupled receptor binding / response to peptide hormone / G protein-coupled receptor activity / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / centriolar satellite / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / 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 / GDP binding / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / sperm principal piece / Thrombin signalling through proteinase activated receptors (PARs) / signaling receptor complex adaptor activity / retina development in camera-type eye / GTPase binding / G protein activity / fibroblast proliferation / Ca2+ pathway / midbody / cell cortex / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / 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 / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / ciliary basal body / G protein-coupled receptor signaling pathway / cell division / lysosomal membrane / GTPase activity / centrosome / synapse / GTP binding / protein-containing complex binding / nucleolus / magnesium ion binding / Golgi apparatus 類似検索 - 分子機能 | |||||||||
| 生物種 | Homo sapiens (ヒト) / synthetic construct (人工物) | |||||||||
| 手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.77 Å | |||||||||
データ登録者 | Hu XL / Wu LJ / Hua T / Liu ZJ | |||||||||
| 資金援助 | 1件
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引用 | ジャーナル: Nature / 年: 2024タイトル: Bitter taste TAS2R14 activation by intracellular tastants and cholesterol. 著者: Xiaolong Hu / Weizhen Ao / Mingxin Gao / Lijie Wu / Yuan Pei / Shenhui Liu / Yiran Wu / Fei Zhao / Qianqian Sun / Junlin Liu / Longquan Jiang / Xin Wang / Yan Li / Qiwen Tan / Jie Cheng / Fan ...著者: Xiaolong Hu / Weizhen Ao / Mingxin Gao / Lijie Wu / Yuan Pei / Shenhui Liu / Yiran Wu / Fei Zhao / Qianqian Sun / Junlin Liu / Longquan Jiang / Xin Wang / Yan Li / Qiwen Tan / Jie Cheng / Fan Yang / Chi Yang / Jinpeng Sun / Tian Hua / Zhi-Jie Liu / ![]() 要旨: Bitter taste receptors, particularly TAS2R14, play central roles in discerning a wide array of bitter substances, ranging from dietary components to pharmaceutical agents. TAS2R14 is also widely ...Bitter taste receptors, particularly TAS2R14, play central roles in discerning a wide array of bitter substances, ranging from dietary components to pharmaceutical agents. TAS2R14 is also widely expressed in extragustatory tissues, suggesting its extra roles in diverse physiological processes and potential therapeutic applications. Here we present cryogenic electron microscopy structures of TAS2R14 in complex with aristolochic acid, flufenamic acid and compound 28.1, coupling with different G-protein subtypes. Uniquely, a cholesterol molecule is observed occupying what is typically an orthosteric site in class A G-protein-coupled receptors. The three potent agonists bind, individually, to the intracellular pockets, suggesting a distinct activation mechanism for this receptor. Comprehensive structural analysis, combined with mutagenesis and molecular dynamic simulation studies, elucidate the broad-spectrum ligand recognition and activation of the receptor by means of intricate multiple ligand-binding sites. Our study also uncovers the specific coupling modes of TAS2R14 with gustducin and G proteins. These findings should be instrumental in advancing knowledge of bitter taste perception and its broader implications in sensory biology and drug discovery. | |||||||||
| 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_38583.map.gz | 56.9 MB | EMDBマップデータ形式 | |
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| ヘッダ (付随情報) | emd-38583-v30.xml emd-38583.xml | 23.8 KB 23.8 KB | 表示 表示 | EMDBヘッダ |
| FSC (解像度算出) | emd_38583_fsc.xml | 8.4 KB | 表示 | FSCデータファイル |
| 画像 | emd_38583.png | 48.3 KB | ||
| Filedesc metadata | emd-38583.cif.gz | 7.8 KB | ||
| その他 | emd_38583_half_map_1.map.gz emd_38583_half_map_2.map.gz | 59.5 MB 59.5 MB | ||
| アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-38583 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-38583 | HTTPS FTP |
-関連構造データ
| 関連構造データ | ![]() 8xqoMC ![]() 8xqlC ![]() 8xqnC ![]() 8xqpC ![]() 8xqrC ![]() 8xqsC ![]() 8xqtC ![]() 8ykyC 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_38583.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: 1.04 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: #2
| ファイル | emd_38583_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_38583_half_map_2.map | ||||||||||||
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| 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 : Structure of human class T GPCR TAS2R14-Gi complex with Aristoloc...
| 全体 | 名称: Structure of human class T GPCR TAS2R14-Gi complex with Aristolochic acid A. |
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| 要素 |
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-超分子 #1: Structure of human class T GPCR TAS2R14-Gi complex with Aristoloc...
| 超分子 | 名称: Structure of human class T GPCR TAS2R14-Gi complex with Aristolochic acid A. 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(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: Homo sapiens (ヒト) |
| 分子量 | 理論値: 42.425125 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MDYKDDDDKE NLYFQSMGCT LSAEDKAAVE RSKMIDRNLR EDGEKAAREV KLLLLGAGES GKSTIVKQMK IIHEAGYSEE ECKQYKAVV YSNTIQSIIA IIRAMGRLKI DFGDSARADD ARQLFVLAGA AEEGFMTAEL AGVIKRLWKD SGVQACFNRS R EYQLNDSA ...文字列: MDYKDDDDKE NLYFQSMGCT LSAEDKAAVE RSKMIDRNLR EDGEKAAREV KLLLLGAGES GKSTIVKQMK IIHEAGYSEE ECKQYKAVV YSNTIQSIIA IIRAMGRLKI DFGDSARADD ARQLFVLAGA AEEGFMTAEL AGVIKRLWKD SGVQACFNRS R EYQLNDSA AYYLNDLDRI AQPNYIPTQQ DVLRTRVKTT GIVETHFTFK DLHFKMFDVG GQRSERKKWI HCFEGVTAII FC VALSDYD LVLAEDEEMN RMHESMKLFD SICNNKWFTD TSIILFLNKK DLFEEKIKKS PLTICYPEYA GSNTYEEAAA YIQ CQFEDL NKRKDTKEIY THFTCATDTK NVQFVFDAVT DVIIKNNLKD CGLF UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1 |
-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: 39.728426 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL ...文字列: MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KLWDVREGMC RQTFTGHESD INAICFFPNG NA FATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYDDFNCNVW DALKADRAGV LAGHDNRVSC LGV TDDGMA VATGSWDSFL KIWNGSSGGG GSGGGGSSGV SGWRLFKKIS UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-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: 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 #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: Homo sapiens (ヒト) |
| 分子量 | 理論値: 30.668211 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MVSAIVLYVL LAAAAHSAFA DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFT ISRDDPKNTL FLQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV M TQATSSVP ...文字列: MVSAIVLYVL LAAAAHSAFA DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFT ISRDDPKNTL FLQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV M TQATSSVP VTPGESVSIS CRSSKSLLHS NGNTYLYWFL QRPGQSPQLL IYRMSNLASG VPDRFSGSGS GTAFTLTISR LE AEDVGVY YCMQHLEYPL TFGAGTKLEL KAAAENLYFQ SHHHHHHHH |
-分子 #5: Exo-alpha-sialidase,Taste receptor type 2 member 14,LgBiT
| 分子 | 名称: Exo-alpha-sialidase,Taste receptor type 2 member 14,LgBiT タイプ: protein_or_peptide / ID: 5 / コピー数: 1 / 光学異性体: LEVO / EC番号: exo-alpha-sialidase |
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| 由来(天然) | 生物種: synthetic construct (人工物) |
| 分子量 | 理論値: 110.840023 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MKTIIALSYI FCLVFADYKD DDDAHHHHHH HHHHENLYFQ SGRAVEGAVK TEPVDLFHPG FLNSSNYRIP ALFKTKEGTL IASIDARRH GGADAPNNDI DTAVRRSEDG GKTWDEGQII MDYPDKSSVI DTTLIQDDET GRIFLLVTHF PSKYGFWNAG L GSGFKNID ...文字列: MKTIIALSYI FCLVFADYKD DDDAHHHHHH HHHHENLYFQ SGRAVEGAVK TEPVDLFHPG FLNSSNYRIP ALFKTKEGTL IASIDARRH GGADAPNNDI DTAVRRSEDG GKTWDEGQII MDYPDKSSVI DTTLIQDDET GRIFLLVTHF PSKYGFWNAG L GSGFKNID GKEYLCLYDS SGKEFTVREN VVYDKDSNKT EYTTNALGDL FKNGTKIDNI NSSTAPLKAK GTSYINLVYS DD DGKTWSE PQNINFQVKK DWMKFLGIAP GRGIQIKNGE HKGRIVVPVY YTNEKGKQSS AVIYSDDSGK NWTIGESPND NRK LENGKI INSKTLSDDA PQLTECQVVE MPNGQLKLFM RNLSGYLNIA TSFDGGATWD ETVEKDTNVL EPYCQLSVIN YSQK VDGKD AVIFSNPNAR SRSNGTVRIG LINQVGTYEN GEPKYEFDWK YNKLVKPGYY AYSCLTELSN GNIGLLYEGT PSEEM SYIE MNLKYLESGA NKGSAGSGGV IKSIFTFVLI VEFIIGNLGN SFIALVNCID WVKGRKISSV DRILTALAIS RISLVW LIF GSWCVSVFFP ALFATEKMFR MLTNIWTVIN HFSVWLATGL GTFYFLKIAN FSNSIFLYLK WRVKKVVLVL LLVTSVF LF LNIALINIHI NASINGYRRN KTCSSDSSNF TRFSSLIVLT STVFIFIPFT LSLAMFLLLI FSMWKHRKKM QHTVKISG D ASTKAHRGVK SVITFFLLYA IFSLSFFISV WTSERLEENL IILSQVMGMA YPSCHSCVLI LGNKKLRQAS LSVLLWLRY MFKDGEPSGH KEFRESSGSG SSGSGSSGSG SSVFTLEDFV GDWEQTAAYN LDQVLEQGGV SSLLQNLAVS VTPIQRIVRS GENALKIDI HVIIPYEGLS ADQMAQIEEV FKVVYPVDDH HFKVILPYGT LVIDGVTPNM LNYFGRPYEG IAVFDGKKIT V TGTLWNGN KIIDERLITP DGSMLFRVTI NS UniProtKB: exo-alpha-sialidase, Taste receptor type 2 member 14 |
-分子 #6: 8-methoxy-6-nitro-naphtho[1,2-e][1,3]benzodioxole-5-carboxylic acid
| 分子 | 名称: 8-methoxy-6-nitro-naphtho[1,2-e][1,3]benzodioxole-5-carboxylic acid タイプ: ligand / ID: 6 / コピー数: 1 / 式: GOQ |
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| 分子量 | 理論値: 341.272 Da |
| Chemical component information | ![]() ChemComp-GOQ: |
-分子 #7: CHOLESTEROL
| 分子 | 名称: CHOLESTEROL / タイプ: ligand / ID: 7 / コピー数: 1 / 式: CLR |
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| 分子量 | 理論値: 386.654 Da |
| Chemical component information | ![]() ChemComp-CLR: |
-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 TITAN KRIOS |
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| 撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (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): 2.0 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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万見について




キーワード
Homo sapiens (ヒト)
データ登録者
引用











































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Y (Row.)
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解析
FIELD EMISSION GUN

