+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-36607 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
タイトル | Cryo-EM structure of the glucagon receptor bound to glucagon and beta-arrestin 1 | |||||||||
マップデータ | ||||||||||
試料 |
| |||||||||
キーワード | Complex structure / glucagon receptor / beta-arrestin 1 / glucagon (グルカゴン) / MEMBRANE PROTEIN (膜タンパク質) | |||||||||
機能・相同性 | 機能・相同性情報 プロテインC / renal water retention / Defective AVP does not bind AVPR2 and causes neurohypophyseal diabetes insipidus (NDI) / positive regulation of establishment of endothelial barrier / Vasopressin-like receptors / regulation of systemic arterial blood pressure by vasopressin / vasopressin receptor activity / glucagon receptor binding / negative regulation of coagulation / regulation of glycogen metabolic process ...プロテインC / renal water retention / Defective AVP does not bind AVPR2 and causes neurohypophyseal diabetes insipidus (NDI) / positive regulation of establishment of endothelial barrier / Vasopressin-like receptors / regulation of systemic arterial blood pressure by vasopressin / vasopressin receptor activity / glucagon receptor binding / negative regulation of coagulation / regulation of glycogen metabolic process / glucagon receptor activity / positive regulation of systemic arterial blood pressure / 止血 / telencephalon development / negative regulation of execution phase of apoptosis / negative regulation of blood coagulation / feeding behavior / : / positive regulation of intracellular signal transduction / response to starvation / cellular response to glucagon stimulus / positive regulation of calcium ion import / エキソサイトーシス / positive regulation of insulin secretion involved in cellular response to glucose stimulus / peptide hormone binding / regulation of insulin secretion / endocytic vesicle / Synthesis, secretion, and deacylation of Ghrelin / Gamma-carboxylation of protein precursors / Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus / Common Pathway of Fibrin Clot Formation / Removal of aminoterminal propeptides from gamma-carboxylated proteins / protein kinase A signaling / positive regulation of gluconeogenesis / positive regulation of vasoconstriction / cellular response to hormone stimulus / activation of adenylate cyclase activity / Intrinsic Pathway of Fibrin Clot Formation / cellular response to starvation / hormone-mediated signaling pathway / response to nutrient / guanyl-nucleotide exchange factor activity / viral budding from plasma membrane / response to activity / positive regulation of peptidyl-threonine phosphorylation / generation of precursor metabolites and energy / response to cytokine / 糖新生 / Cell surface interactions at the vascular wall / peptide binding / Post-translational protein phosphorylation / clathrin-coated endocytic vesicle membrane / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / adenylate cyclase-activating G protein-coupled receptor signaling pathway / Glucagon signaling in metabolic regulation / hormone activity / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / 血圧 / negative regulation of inflammatory response / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Golgi lumen / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / 凝固・線溶系 / Cargo recognition for clathrin-mediated endocytosis / glucose homeostasis / positive regulation of peptidyl-serine phosphorylation / Clathrin-mediated endocytosis / G alpha (s) signalling events / G alpha (q) signalling events / clathrin-dependent endocytosis of virus by host cell / secretory granule lumen / cell surface receptor signaling pathway / positive regulation of ERK1 and ERK2 cascade / host cell surface receptor binding / エンドソーム / G protein-coupled receptor signaling pathway / fusion of virus membrane with host plasma membrane / negative regulation of cell population proliferation / 小胞体 / signaling receptor binding / serine-type endopeptidase activity / fusion of virus membrane with host endosome membrane / エンベロープ (ウイルス) / calcium ion binding / positive regulation of cell population proliferation / virion attachment to host cell / positive regulation of gene expression / negative regulation of apoptotic process / host cell plasma membrane / perinuclear region of cytoplasm / virion membrane / ゴルジ体 / 小胞体 / タンパク質分解 / extracellular space / extracellular region / 生体膜 / identical protein binding 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / Escherichia phage EcSzw-2 (ファージ) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.3 Å | |||||||||
データ登録者 | Chen K / Zhang C / Lin S / Zhao Q / Wu B | |||||||||
資金援助 | 中国, 2件
| |||||||||
引用 | ジャーナル: Nature / 年: 2023 タイトル: Tail engagement of arrestin at the glucagon receptor. 著者: Kun Chen / Chenhui Zhang / Shuling Lin / Xinyu Yan / Heng Cai / Cuiying Yi / Limin Ma / Xiaojing Chu / Yuchen Liu / Ya Zhu / Shuo Han / Qiang Zhao / Beili Wu / 要旨: Arrestins have pivotal roles in regulating G protein-coupled receptor (GPCR) signalling by desensitizing G protein activation and mediating receptor internalization. It has been proposed that the ...Arrestins have pivotal roles in regulating G protein-coupled receptor (GPCR) signalling by desensitizing G protein activation and mediating receptor internalization. It has been proposed that the arrestin binds to the receptor in two different conformations, 'tail' and 'core', which were suggested to govern distinct processes of receptor signalling and trafficking. However, little structural information is available for the tail engagement of the arrestins. Here we report two structures of the glucagon receptor (GCGR) bound to β-arrestin 1 (βarr1) in glucagon-bound and ligand-free states. These structures reveal a receptor tail-engaged binding mode of βarr1 with many unique features, to our knowledge, not previously observed. Helix VIII, instead of the receptor core, has a major role in accommodating βarr1 by forming extensive interactions with the central crest of βarr1. The tail-binding pose is further defined by a close proximity between the βarr1 C-edge and the receptor helical bundle, and stabilized by a phosphoinositide derivative that bridges βarr1 with helices I and VIII of GCGR. Lacking any contact with the arrestin, the receptor core is in an inactive state and loosely binds to glucagon. Further functional studies suggest that the tail conformation of GCGR-βarr governs βarr recruitment at the plasma membrane and endocytosis of GCGR, and provides a molecular basis for the receptor forming a super-complex simultaneously with G protein and βarr to promote sustained signalling within endosomes. These findings extend our knowledge about the arrestin-mediated modulation of GPCR functionalities. | |||||||||
履歴 |
|
-構造の表示
添付画像 |
---|
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_36607.map.gz | 57.3 MB | EMDBマップデータ形式 | |
---|---|---|---|---|
ヘッダ (付随情報) | emd-36607-v30.xml emd-36607.xml | 18.4 KB 18.4 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_36607.png | 46.9 KB | ||
その他 | emd_36607_half_map_1.map.gz emd_36607_half_map_2.map.gz | 59.4 MB 59.3 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-36607 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36607 | HTTPS FTP |
-関連構造データ
関連構造データ | 8jrvMC 8jruC 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) |
---|---|
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 |
---|---|
「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_36607.map.gz / 形式: CCP4 / 大きさ: 64 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
ボクセルのサイズ | X=Y=Z: 1.071 Å | ||||||||||||||||||||
密度 |
| ||||||||||||||||||||
対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
|
-添付データ
-ハーフマップ: #2
ファイル | emd_36607_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_36607_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-試料の構成要素
-全体 : The glucagon receptor bound to glucagon and beta-arrestin 1
全体 | 名称: The glucagon receptor bound to glucagon and beta-arrestin 1 |
---|---|
要素 |
|
-超分子 #1: The glucagon receptor bound to glucagon and beta-arrestin 1
超分子 | 名称: The glucagon receptor bound to glucagon and beta-arrestin 1 タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#4 |
---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: HA signal peptide,HPC4 purification tag,Glucagon receptor,C-termi...
分子 | 名称: HA signal peptide,HPC4 purification tag,Glucagon receptor,C-terminal tail of Vasopressin V2 receptor タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 54.163012 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MKTIIALSYI FCLVFAGAPE DQVDPRLIDG KGSGSAGSAG SQVMDFLFEK WKLYGDQCHH NLSLLPPPTE LVCNRTFDKY SCWPDTPAN TTANISCPWY LPWHHKVQHR FVFKRCGPDG QWVRGPRGQP WRDASQCQMD GEEIEVQKEV AKMYSSFQVM Y TVGYSLSL ...文字列: MKTIIALSYI FCLVFAGAPE DQVDPRLIDG KGSGSAGSAG SQVMDFLFEK WKLYGDQCHH NLSLLPPPTE LVCNRTFDKY SCWPDTPAN TTANISCPWY LPWHHKVQHR FVFKRCGPDG QWVRGPRGQP WRDASQCQMD GEEIEVQKEV AKMYSSFQVM Y TVGYSLSL GALLLALAIL GGLSKLHCTR NAIHANLFAS FVLKASSVLV IDGLLRTRYS QKIGDDLSVS TWLSDGAVAG CR VAAVFMQ YGIVANYCWL LVEGLYLHNL LGLATLPERS FFSLYLGIGW GAPMLFVVPW AVVKCLFENV QCWTSNDNMG FWW ILRFPV FLAILINFFI FVRIVQLLVA KLRARQMHHT DYKFRLAKST LTLIPLLGVH EVVFAFVTDE HAQGTLRSAK LFFD LFLSS FQGLLVAVLY CFLNKEVQSE LRRRWHRWRL GKVLWEERNT SNARGRTPPS LGPQDE(SEP)CT(TPO) A(SEP) (SEP)(SEP)LAKDT SS UniProtKB: ヘマグルチニン, Vitamin K-dependent protein C, Glucagon receptor, Vasopressin V2 receptor |
-分子 #2: Glucagon
分子 | 名称: Glucagon / タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 3.486781 KDa |
配列 | 文字列: HSQGTFTSDY SKYLDSRRAQ DFVQWLMNT UniProtKB: Pro-glucagon |
-分子 #3: Beta-arrestin 1 and single-chain fragment variable 30 (scFv30)
分子 | 名称: Beta-arrestin 1 and single-chain fragment variable 30 (scFv30) タイプ: protein_or_peptide / ID: 3 / コピー数: 3 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 69.173891 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MGDKGTRVFK KASPNGKLTV YLGKRDFVDH IDLVEPVDGV VLVDPEYLKE RRVYVTLTAA FRYGREDLDV LGLTFRKDLF VANVQSFPP APEDKKPLTR LQERLIKKLG EHAYPFTFEI PPNLPSSVTL QPGPEDTGKA IGVDYEVKAF VAENLEEKIH K RNSVRLVI ...文字列: MGDKGTRVFK KASPNGKLTV YLGKRDFVDH IDLVEPVDGV VLVDPEYLKE RRVYVTLTAA FRYGREDLDV LGLTFRKDLF VANVQSFPP APEDKKPLTR LQERLIKKLG EHAYPFTFEI PPNLPSSVTL QPGPEDTGKA IGVDYEVKAF VAENLEEKIH K RNSVRLVI EKVQYAPERP GPQPTAETTR QFLMSDKPLH LEASLDKEIY YHGEPISVNV HVTNNTNKTV KKIKISVRQY AD IVLFNTA QYKVPVAMEE ADDTVAPSST FSKVYTLTPF LANNREKRGL ALDGKLKHED TNLASSTLLR EGANREILGI IVS YKVKVK LVVSRGGLLG DLASSDVAVE LPFTLMHPKP KEEPPHREVP EHETPVDTNL SDIQMTQSPS SLSASVGDRV TITC RASQS VSSAVAWYQQ KPGKAPKLLI YSASSLYSGV PSRFSGSRSG TDFTLTISSL QPEDFATYYC QQYKYVPVTF GQGTK VEIK GTTAASGSSG GSSSGAEVQL VESGGGLVQP GGSLRLSCAA SGFNVYSSSI HWVRQAPGKG LEWVASISSY YGYTYY ADS VKGRFTISAD TSKNTAYLQM NSLRAEDTAV YYCARSRQFW YSGLDYWGQG TLVTVSSAHH HHHH |
-分子 #4: Nanobody 32
分子 | 名称: Nanobody 32 / タイプ: protein_or_peptide / ID: 4 / コピー数: 1 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: Escherichia phage EcSzw-2 (ファージ) |
分子量 | 理論値: 13.867408 KDa |
組換発現 | 生物種: Escherichia coli BL21 (大腸菌) |
配列 | 文字列: MAQVQLQESG GGLVQAGGSL RLSCVVSGFF FDTVTMAWYR RAPGKHRELV ASATAGGTTT YADSVKDRFT ISRDNAKNTV YLQMNSLKP EDTAVYYCNT FVRSLSWGQG TQVTVSSHHH HHHEPEA |
-分子 #5: [(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(o...
分子 | 名称: [(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-propyl] octanoate タイプ: ligand / ID: 5 / コピー数: 1 / 式: PIO |
---|---|
分子量 | 理論値: 746.566 Da |
Chemical component information | ChemComp-PIO: |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
---|---|
解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
濃度 | 6 mg/mL |
---|---|
緩衝液 | pH: 7.5 |
凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
---|---|
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: SPOT SCAN / 撮影モード: BRIGHT FIELDBright-field microscopy / 最大 デフォーカス(公称値): 1.5 µm / 最小 デフォーカス(公称値): 0.8 µm |
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: 70.0 e/Å2 |
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: INSILICO MODEL |
---|---|
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 300738 |