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基本情報
登録情報 | ![]() | |||||||||||||||
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タイトル | Cryo-EM structure of peptide free and Gs-coupled GIPR | |||||||||||||||
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![]() | Glucose-dependent insulinotropic polypeptide receptor / cryo-electron microscopy / G protein-coupled receptor / ligand recognition / STRUCTURAL PROTEIN | |||||||||||||||
機能・相同性 | ![]() gastric inhibitory peptide receptor activity / glucagon family peptide binding / gastric inhibitory peptide signaling pathway / desensitization of G protein-coupled receptor signaling pathway / sensory perception of chemical stimulus / endocrine pancreas development / 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 / desensitization of G protein-coupled receptor signaling pathway / sensory perception of chemical stimulus / endocrine pancreas development / positive regulation of cAMP-mediated signaling / mu-type opioid receptor binding / response to fatty acid / corticotropin-releasing hormone receptor 1 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 / 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 / Ca2+ pathway / 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 / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / alkylglycerophosphoethanolamine phosphodiesterase activity / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / G alpha (z) signalling events / Extra-nuclear estrogen signaling / beta-2 adrenergic receptor binding / 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 / spectrin binding / Vasopressin regulates renal water homeostasis via Aquaporins / peptide hormone binding / regulation of insulin secretion / photoreceptor outer segment / D1 dopamine receptor binding / response to axon injury / generation of precursor metabolites and energy / response to glucose / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / response to nutrient / cardiac muscle cell apoptotic process / insulin-like growth factor receptor binding / adenylate cyclase activator activity / ionotropic glutamate receptor binding / photoreceptor inner segment / response to calcium ion / G-protein beta/gamma-subunit complex binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / positive regulation of insulin secretion / adenylate cyclase-activating G protein-coupled receptor signaling pathway / transmembrane signaling receptor activity / Glucagon-type ligand receptors / cellular response to catecholamine stimulus / sensory perception of taste / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / signaling receptor complex adaptor activity / GTPase binding / retina development in camera-type eye / cellular response to hypoxia / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / 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 | ![]() ![]() ![]() ![]() | |||||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.86 Å | |||||||||||||||
![]() | Cong ZT / Zhao FH / Li Y / Luo G / Zhou QT / Yang DH / Wang MW / Dai AT / Shen DD / Zhang Y ...Cong ZT / Zhao FH / Li Y / Luo G / Zhou QT / Yang DH / Wang MW / Dai AT / Shen DD / Zhang Y / Xia T / Stevens RC / Xu HE / Zhao LH | |||||||||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Molecular features of the ligand-free GLP-1R, GCGR and GIPR in complex with G proteins. 著者: Zhaotong Cong / Fenghui Zhao / Yang Li / Gan Luo / Yiting Mai / Xianyue Chen / Yanyan Chen / Shi Lin / Xiaoqing Cai / Qingtong Zhou / Dehua Yang / Ming-Wei Wang / ![]() ![]() 要旨: Class B1 G protein-coupled receptors (GPCRs) are important regulators of many physiological functions such as glucose homeostasis, which is mainly mediated by three peptide hormones, i.e., glucagon- ...Class B1 G protein-coupled receptors (GPCRs) are important regulators of many physiological functions such as glucose homeostasis, which is mainly mediated by three peptide hormones, i.e., glucagon-like peptide-1 (GLP-1), glucagon (GCG), and glucose-dependent insulinotropic polypeptide (GIP). They trigger a cascade of signaling events leading to the formation of an active agonist-receptor-G protein complex. However, intracellular signal transducers can also activate the receptor independent of extracellular stimuli, suggesting an intrinsic role of G proteins in this process. Here, we report cryo-electron microscopy structures of the human GLP-1 receptor (GLP-1R), GCG receptor (GCGR), and GIP receptor (GIPR) in complex with G proteins without the presence of cognate ligands. These ligand-free complexes share a similar intracellular architecture to those bound by endogenous peptides, in which, the G protein alone directly opens the intracellular binding cavity and rewires the extracellular orthosteric pocket to stabilize the receptor in a state unseen before. While the peptide-binding site is partially occupied by the inward folded transmembrane helix 6 (TM6)-extracellular loop 3 (ECL3) juncture of GIPR or a segment of GCGR ECL2, the extracellular portion of GLP-1R adopts a conformation close to the active state. Our findings offer valuable insights into the distinct activation mechanisms of these three important receptors. It is possible that in the absence of a ligand, the intracellular half of transmembrane domain is mobilized with the help of G protein, which in turn rearranges the extracellular half to form a transitional conformation, facilitating the entry of the peptide N-terminus. | |||||||||||||||
履歴 |
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マップデータ | ![]() | 32.6 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 20.5 KB 20.5 KB | 表示 表示 | ![]() |
画像 | ![]() | 34.6 KB | ||
Filedesc metadata | ![]() | 6.8 KB | ||
その他 | ![]() ![]() | 59.3 MB 59.3 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
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リンク
EMDBのページ | ![]() ![]() |
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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 | ![]() | ||||||||||||||||||||
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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_37390_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_37390_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 : Cryo-EM structure of the human glucose-dependent insulinotropic p...
全体 | 名称: Cryo-EM structure of the human glucose-dependent insulinotropic polypeptide receptor in complex with GIP and G protein |
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要素 |
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-超分子 #1: Cryo-EM structure of the human glucose-dependent insulinotropic p...
超分子 | 名称: Cryo-EM structure of the human glucose-dependent insulinotropic polypeptide receptor in complex with GIP and G 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: ![]() |
-分子 #1: Gastric inhibitory polypeptide receptor,Fusion protein
分子 | 名称: Gastric inhibitory polypeptide receptor,Fusion protein 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: 64.950695 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: RAETGSKGQT AGELYQRWER YRRECQETLA AAEPPSGLAC NGSFDMYVCW DYAAPNATAR ASCPWYLPWH HHVAAGFVLR QCGSDGQWG LWRDHTQCEN PEKNEAFLDQ RLILERLQVM YTVGYSLSLA TLLLALLILS LFRRLHCTRN YIHINLFTSF M LRAAAILS ...文字列: RAETGSKGQT AGELYQRWER YRRECQETLA AAEPPSGLAC NGSFDMYVCW DYAAPNATAR ASCPWYLPWH HHVAAGFVLR QCGSDGQWG LWRDHTQCEN PEKNEAFLDQ RLILERLQVM YTVGYSLSLA TLLLALLILS LFRRLHCTRN YIHINLFTSF M LRAAAILS RDRLLPRPGP YLGDQALALW NQALAACRTA QIVTQYCVGA NYTWLLVEGV YLHSLLVLVG GSEEGHFRYY LL LGWGAPA LFVIPWVIVR YLYENTQCWE RNEVKAIWWI IRTPILMTIL INFLIFIRIL GILLSKLRTR QMRCRDYRLR LAR STLFLV PLLGVHEVVF APVTEEQARG ALRFAKLGFE IFLSSFQGFL VSVLYCFINK EVQSEIRRGW HHCRLRRSLG EEQR GSSGG GGSGGGGSSG VFTLEDFVGD WEQTAAYNLD QVLEQGGVSS LLQNLAVSVT PIQRIVRSGE NALKIDIHVI IPYEG LSAD QMAQIEEVFK VVYPVDDHHF KVILPYGTLV IDGVTPNMLN YFGRPYEGIA VFDGKKITVT GTLWNGNKII DERLIT PDG SMLFRVTINS 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: ![]() ![]() |
分子量 | 理論値: 45.743441 KDa |
組換発現 | 生物種: ![]() ![]() |
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 HYCYPHFTCS 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,O-antigen polymerase 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: 40.226992 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 WDSFLKIWNG SSGGGGSGGG GSSGVSGWRL FKKIS UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, O-antigen polymerase |
-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: ![]() ![]() |
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: 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: 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 |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 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: 7.4 |
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凍結 | 凍結剤: ETHANE |
詳細 | Cryo-EM structure of peptide free and Gs-coupled GIPR |
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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 (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 |
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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: 詳細: and 2QKH |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 2.86 Å / 解像度の算出法: OTHER / 使用した粒子像数: 807839 |
初期 角度割当 | タイプ: OTHER |
最終 角度割当 | タイプ: OTHER |