+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-35707 | |||||||||||||||||||||
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タイトル | Cryo-EM structure of GIPR splice variant 2 (SV2) in complex with Gs protein | |||||||||||||||||||||
マップデータ | ||||||||||||||||||||||
試料 |
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キーワード | Cryo-electron microscopy / G protein-coupled receptor / splice variant / receptor activation. / STRUCTURAL PROTEIN | |||||||||||||||||||||
機能・相同性 | 機能・相同性情報 gastric inhibitory peptide receptor activity / glucagon family peptide binding / gastric inhibitory peptide signaling pathway / endocrine pancreas development / desensitization of G protein-coupled receptor signaling pathway / sensory perception of chemical stimulus / positive regulation of cAMP-mediated signaling / mu-type opioid receptor binding / response to fatty acid / corticotropin-releasing hormone receptor 1 binding ...gastric inhibitory peptide receptor activity / glucagon family peptide binding / gastric inhibitory peptide signaling pathway / endocrine pancreas development / desensitization of G protein-coupled receptor signaling pathway / sensory perception of chemical stimulus / positive regulation of cAMP-mediated signaling / mu-type opioid receptor binding / response to fatty acid / corticotropin-releasing hormone receptor 1 binding / D1 dopamine receptor binding / 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 / Ca2+ pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / G protein-coupled peptide receptor activity / Activation of G protein gated Potassium channels / 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 / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / G alpha (i) signalling events / 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 / Glucagon-type ligand receptors / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Adrenaline,noradrenaline inhibits insulin secretion / alkylglycerophosphoethanolamine phosphodiesterase activity / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / beta-2 adrenergic receptor binding / Extra-nuclear estrogen signaling / G alpha (z) signalling events / G alpha (s) signalling events / G alpha (q) signalling events / photoreceptor outer segment membrane / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / activation of adenylate cyclase activity / spectrin binding / Vasopressin regulates renal water homeostasis via Aquaporins / adenylate cyclase-activating adrenergic receptor signaling pathway / adenylate cyclase activator activity / regulation of insulin secretion / peptide hormone binding / photoreceptor outer segment / response to axon injury / response to glucose / cardiac muscle cell apoptotic process / insulin-like growth factor receptor binding / ionotropic glutamate receptor binding / photoreceptor inner segment / G-protein beta/gamma-subunit complex binding / response to nutrient / generation of precursor metabolites and energy / adenylate cyclase-activating G protein-coupled receptor signaling pathway / positive regulation of insulin secretion / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / Glucagon-type ligand receptors / response to calcium ion / cellular response to catecholamine stimulus / sensory perception of taste / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / transmembrane signaling receptor activity / G-protein beta-subunit binding / heterotrimeric G-protein complex / signaling receptor complex adaptor activity / GTPase binding / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / cellular response to hypoxia / cell body / G alpha (s) signalling events / cell population proliferation / cell surface receptor signaling pathway / G protein-coupled receptor signaling pathway / GTPase activity / dendrite 類似検索 - 分子機能 | |||||||||||||||||||||
生物種 | Homo sapiens (ヒト) / Bos taurus (ウシ) / Rattus norvegicus (ドブネズミ) / 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: 3.13 Å | |||||||||||||||||||||
データ登録者 | Zhao FH / Hang KN / Zhou QT / Shao LJ / Li H / Li WZ / Lin S / Dai AT / Cai XQ / Liu YY ...Zhao FH / Hang KN / Zhou QT / Shao LJ / Li H / Li WZ / Lin S / Dai AT / Cai XQ / Liu YY / Xu YN / Feng WB / Yang DH / Wang MW | |||||||||||||||||||||
資金援助 | 中国, 6件
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引用 | ジャーナル: Proc Natl Acad Sci U S A / 年: 2023 タイトル: Molecular basis of signal transduction mediated by the human GIPR splice variants. 著者: Fenghui Zhao / Kaini Hang / Qingtong Zhou / Lijun Shao / Hao Li / Wenzhuo Li / Shi Lin / Antao Dai / Xiaoqing Cai / Yanyun Liu / Yingna Xu / Wenbo Feng / Dehua Yang / Ming-Wei Wang / 要旨: Glucose-dependent insulinotropic polypeptide receptor (GIPR) is a potential drug target for metabolic disorders. It works with glucagon-like peptide-1 receptor and glucagon receptor in humans to ...Glucose-dependent insulinotropic polypeptide receptor (GIPR) is a potential drug target for metabolic disorders. It works with glucagon-like peptide-1 receptor and glucagon receptor in humans to maintain glucose homeostasis. Unlike the other two receptors, GIPR has at least 13 reported splice variants (SVs), more than half of which have sequence variations at either C or N terminus. To explore their roles in endogenous peptide-mediated GIPR signaling, we determined the cryoelectron microscopy (cryo-EM) structures of the two N terminus-altered SVs (referred as GIPR-202 and GIPR-209 in the Ensembl database, SV1 and SV2 here, respectively) and investigated the outcome of coexpressing each of them in question with GIPR in HEK293T cells with respect to ligand binding, receptor expression, cAMP (adenosine 3,5-cyclic monophosphate) accumulation, β-arrestin recruitment, and cell surface localization. It was found that while both N terminus-altered SVs of GIPR neither bound to the hormone nor elicited signal transduction per se, they suppressed ligand binding and cAMP accumulation of GIPR. Meanwhile, SV1 reduced GIPR-mediated β-arrestin 2 responses. The cryo-EM structures of SV1 and SV2 showed that they reorganized the extracellular halves of transmembrane helices 1, 6, and 7 and extracellular loops 2 and 3 to adopt a ligand-binding pocket-occupied conformation, thereby losing binding ability to the peptide. The results suggest a form of signal bias that is constitutive and ligand-independent, thus expanding our knowledge of biased signaling beyond pharmacological manipulation (i.e., ligand specific) as well as constitutive and ligand-independent (e.g., SV1 of the growth hormone-releasing hormone receptor). | |||||||||||||||||||||
履歴 |
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-構造の表示
添付画像 |
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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_35707.map.gz | 59.7 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-35707-v30.xml emd-35707.xml | 20.6 KB 20.6 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_35707.png | 32.9 KB | ||
Filedesc metadata | emd-35707.cif.gz | 6.5 KB | ||
その他 | emd_35707_half_map_1.map.gz emd_35707_half_map_2.map.gz | 59.2 MB 59.2 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-35707 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-35707 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_35707_validation.pdf.gz | 722.1 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_35707_full_validation.pdf.gz | 721.7 KB | 表示 | |
XML形式データ | emd_35707_validation.xml.gz | 12.4 KB | 表示 | |
CIF形式データ | emd_35707_validation.cif.gz | 14.5 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35707 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35707 | HTTPS FTP |
-関連構造データ
関連構造データ | 8itmMC 8itlC 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 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-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_35707.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_35707_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_35707_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 |
-試料の構成要素
-全体 : Cryo-EM structure of a splice variant of the GIPR(SV2) in complex...
全体 | 名称: Cryo-EM structure of a splice variant of the GIPR(SV2) in complex with Gs protein |
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要素 |
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-超分子 #1: Cryo-EM structure of a splice variant of the GIPR(SV2) in complex...
超分子 | 名称: Cryo-EM structure of a splice variant of the GIPR(SV2) in complex with Gs protein タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Gastric inhibitory polypeptide receptor
分子 | 名称: Gastric inhibitory polypeptide receptor / 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: 41.358254 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MNSAHCNFRL PGSSDSPASA SREAGITEAG ITVAAGFVLR QCGSDGQWGL WRDHTQCENP EKNEAFLDQR LILERLQVMY TVGYSLSLA TLLLALLILS LFRRLHCTRN YIHINLFTSF MLRAAAILSR DRLLPRPGPY LGDQALALWN QALAACRTAQ I VTQYCVGA ...文字列: MNSAHCNFRL PGSSDSPASA SREAGITEAG ITVAAGFVLR QCGSDGQWGL WRDHTQCENP EKNEAFLDQR LILERLQVMY TVGYSLSLA TLLLALLILS LFRRLHCTRN YIHINLFTSF MLRAAAILSR DRLLPRPGPY LGDQALALWN QALAACRTAQ I VTQYCVGA NYTWLLVEGV YLHSLLVLVG GSEEGHFRYY LLLGWGAPAL FVIPWVIVRY LYENTQCWER NEVKAIWWII RT PILMTIL INFLIFIRIL GILLSKLRTR QMRCRDYRLR LARSTLFLVP LLGVHEVVFA PVTEEQARGA LRFAKLGFEI FLS SFQGFL VSVLYCFINK EVQSEIRRGW HHCRLRRSLG EEQR UniProtKB: Gastric inhibitory polypeptide receptor |
-分子 #2: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
分子 | 名称: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short 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: Bos taurus (ウシ) |
分子量 | 理論値: 45.727441 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MGCLGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGAGE SGKNTIVKQM RILHVNGFNG EGGEEDPQAA RSNSDGEKA TKVQDIKNNL KEAIETIVAA MSNLVPPVEL ANPENQFRVD YILSVMNVPD FDFPPEFYEH AKALWEDEGV R ACYERSNE ...文字列: MGCLGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGAGE SGKNTIVKQM RILHVNGFNG EGGEEDPQAA RSNSDGEKA TKVQDIKNNL KEAIETIVAA MSNLVPPVEL ANPENQFRVD YILSVMNVPD FDFPPEFYEH AKALWEDEGV R ACYERSNE YQLIDCAQYF LDKIDVIKQD DYVPSDQDLL RCRVLTSGIF ETKFQVDKVN FHMFDVGAQR DERRKWIQCF ND VTAIIFV VASSSYNMVI REDNQTNRLQ AALKLFDSIW NNKWLRDTSV ILFLNKQDLL AEKVLAGKSK IEDYFPEFAR YTT PEDATP EPGEDPRVTR AKYFIRDEFL RISTASGDGR HYCYPHFTCA VDTENIRRVF NDCRDIIQRM HLRQYELL UniProtKB: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short |
-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: 40.226992 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
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 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: Bos taurus (ウシ) |
分子量 | 理論値: 7.861143 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
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: Nanobody-35
分子 | 名称: Nanobody-35 / 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: synthetic construct (人工物) |
分子量 | 理論値: 13.885439 KDa |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: QVQLQESGGG LVQPGGSLRL SCAASGFTFS NYKMNWVRQA PGKGLEWVSD ISQSGASISY TGSVKGRFTI SRDNAKNTLY LQMNSLKPE DTAVYYCARC PAPFTRDCFD VTSTTYAYRG QGTQVTVSS |
-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 |
-試料調製
緩衝液 | pH: 7.4 |
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凍結 | 凍結剤: ETHANE |
-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: 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): 2.2 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 |
-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: 3.13 Å / 解像度の算出法: DIFFRACTION PATTERN/LAYERLINES / 使用した粒子像数: 463406 |
初期 角度割当 | タイプ: OTHER |
最終 角度割当 | タイプ: OTHER |