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基本情報
登録情報 | データベース: EMDB / ID: EMD-0917 | |||||||||||||||||||||||||||
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タイトル | Cryo-EM structure of the human glucagon receptor in complex with Gs | |||||||||||||||||||||||||||
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![]() | glucagon receptor / GPCR / Gs protein / SIGNALING PROTEIN | |||||||||||||||||||||||||||
機能・相同性 | ![]() glucagon receptor binding / regulation of glycogen metabolic process / glucagon receptor activity / protein kinase A signaling / negative regulation of execution phase of apoptosis / feeding behavior / response to starvation / positive regulation of calcium ion import / exocytosis / peptide hormone binding ...glucagon receptor binding / regulation of glycogen metabolic process / glucagon receptor activity / protein kinase A signaling / negative regulation of execution phase of apoptosis / feeding behavior / response to starvation / positive regulation of calcium ion import / exocytosis / peptide hormone binding / positive regulation of insulin secretion involved in cellular response to glucose stimulus / PKA activation in glucagon signalling / Synthesis, secretion, and deacylation of Ghrelin / hair follicle placode formation / developmental growth / D1 dopamine receptor binding / intracellular transport / vascular endothelial cell response to laminar fluid shear stress / renal water homeostasis / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / hormone-mediated signaling pathway / response to nutrient / positive regulation of gluconeogenesis / regulation of insulin secretion / cellular response to glucagon stimulus / adenylate cyclase activator activity / guanyl-nucleotide exchange factor activity / cellular response to starvation / trans-Golgi network membrane / response to activity / gluconeogenesis / generation of precursor metabolites and energy / negative regulation of inflammatory response to antigenic stimulus / hormone activity / bone development / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / regulation of blood pressure / G-protein beta/gamma-subunit complex binding / platelet aggregation / Olfactory Signaling Pathway / cognition / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / adenylate cyclase-activating dopamine receptor signaling pathway / sensory perception of smell / GPER1 signaling / Inactivation, recovery and regulation of the phototransduction cascade / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / glucose homeostasis / heterotrimeric G-protein complex / G alpha (12/13) signalling events / sensory perception of taste / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / positive regulation of cold-induced thermogenesis / G protein activity / GTPase binding / Ca2+ pathway / retina development in camera-type eye / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / fibroblast proliferation / G alpha (i) signalling events / secretory granule lumen / 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 / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell population proliferation / cell surface receptor signaling pathway 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: 3.7 Å | |||||||||||||||||||||||||||
![]() | Qiao A / Han S | |||||||||||||||||||||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural basis of G and G recognition by the human glucagon receptor. 著者: Anna Qiao / Shuo Han / Xinmei Li / Zhixin Li / Peishen Zhao / Antao Dai / Rulve Chang / Linhua Tai / Qiuxiang Tan / Xiaojing Chu / Limin Ma / Thor Seneca Thorsen / Steffen Reedtz-Runge / ...著者: Anna Qiao / Shuo Han / Xinmei Li / Zhixin Li / Peishen Zhao / Antao Dai / Rulve Chang / Linhua Tai / Qiuxiang Tan / Xiaojing Chu / Limin Ma / Thor Seneca Thorsen / Steffen Reedtz-Runge / Dehua Yang / Ming-Wei Wang / Patrick M Sexton / Denise Wootten / Fei Sun / Qiang Zhao / Beili Wu / ![]() ![]() ![]() 要旨: Class B G protein-coupled receptors, an important class of therapeutic targets, signal mainly through the G class of heterotrimeric G proteins, although they do display some promiscuity in G protein ...Class B G protein-coupled receptors, an important class of therapeutic targets, signal mainly through the G class of heterotrimeric G proteins, although they do display some promiscuity in G protein binding. Using cryo-electron microscopy, we determined the structures of the human glucagon receptor (GCGR) bound to glucagon and distinct classes of heterotrimeric G proteins, G or G These two structures adopt a similar open binding cavity to accommodate G and G The G binding selectivity of GCGR is explained by a larger interaction interface, but there are specific interactions that affect G more than G binding. Conformational differences in the receptor intracellular loops were found to be key selectivity determinants. These distinctions in transducer engagement were supported by mutagenesis and functional studies. | |||||||||||||||||||||||||||
履歴 |
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構造の表示
ムービー |
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構造ビューア | EMマップ: ![]() ![]() ![]() |
添付画像 |
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-EMDBアーカイブ
マップデータ | ![]() | 58.8 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 18.3 KB 18.3 KB | 表示 表示 | ![]() |
画像 | ![]() | 45.5 KB | ||
マスクデータ | ![]() | 64 MB | ![]() | |
Filedesc metadata | ![]() | 6.6 KB | ||
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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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: 0.82 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-マスク #1
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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 : Complex of glucagon receptor bound to glucagon, Gs protein and na...
全体 | 名称: Complex of glucagon receptor bound to glucagon, Gs protein and nanobody |
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要素 |
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-超分子 #1: Complex of glucagon receptor bound to glucagon, Gs protein and na...
超分子 | 名称: Complex of glucagon receptor bound to glucagon, Gs protein and nanobody 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: 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: 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: 45.683434 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 LDKIDVIKQA 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 #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: ![]() |
分子量 | 理論値: 38.744371 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MHHHHHHGSL LQSELDQLRQ EAEQLKNQIR DARKACADAT LSQITNNIDP VGRIQMRTRR TLRGHLAKIY AMHWGTDSRL LVSASQDGK LIIWDSYTTN KVHAIPLRSS WVMTCAYAPS GNYVACGGLD NICSIYNLKT REGNVRVSRE LAGHTGYLSC C RFLDDNQI ...文字列: MHHHHHHGSL LQSELDQLRQ EAEQLKNQIR DARKACADAT LSQITNNIDP VGRIQMRTRR TLRGHLAKIY AMHWGTDSRL LVSASQDGK LIIWDSYTTN KVHAIPLRSS WVMTCAYAPS GNYVACGGLD NICSIYNLKT REGNVRVSRE LAGHTGYLSC C RFLDDNQI VTSSGDTTCA LWDIETGQQT TTFTGHTGDV MSLSLAPDTR LFVSGACDAS AKLWDVREGM CRQTFTGHES DI NAICFFP NGNAFATGSD DATCRLFDLR ADQELMTYSH DNIICGITSV SFSKSGRLLL AGYDDFNCNV WDALKADRAG VLA GHDNRV SCLGVTDDGM AVATGSWDSF LKIWN 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: ![]() |
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: Nb35
分子 | 名称: Nb35 / 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: 15.140742 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: QVQLQESGGG LVQPGGSLRL SCAASGFTFS NYKMNWVRQA PGKGLEWVSD ISQSGASISY TGSVKGRFTI SRDNAKNTLY LQMNSLKPE DTAVYYCARC PAPFTRDCFD VTSTTYAYRG QGTQVTVSSH HHHHHEPEA |
-分子 #5: Glucagon receptor
分子 | 名称: Glucagon receptor / 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: 48.398109 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: QVMDFLFEKW KLYGDQCHHN LSLLPPPTEL VCNRTFDKYS CWPDTPANTT ANISCPWYLP WHHKVQHRFV FKRCGPDGQW VRGPRGQPW RDASQCQMDG EEIEVQKEVA KMYSSFQVMY TVGYSLSLGA LLLALAILGG LSKLHCTRNA IHANLFASFV L KASSVLVI ...文字列: QVMDFLFEKW KLYGDQCHHN LSLLPPPTEL VCNRTFDKYS CWPDTPANTT ANISCPWYLP WHHKVQHRFV FKRCGPDGQW VRGPRGQPW RDASQCQMDG EEIEVQKEVA KMYSSFQVMY TVGYSLSLGA LLLALAILGG LSKLHCTRNA IHANLFASFV L KASSVLVI DGLLRTRYSQ KIGDDLSVST WLSDGAVAGC RVAAVFMQYG IVANYCWLLV EGLYLHNLLG LATLPERSFF SL YLGIGWG APMLFVVPWA VVKCLFENVQ CWTSNDNMGF WWILRFPVFL AILINFFIFV RIVQLLVAKL RARQMHHTDY KFR LAKSTL TLIPLLGVHE VVFAFVTDEH AQGTLRSAKL FFDLFLSSFQ GLLVAVLYCF LNKEVQSELR RRWHRWRLGK VLWE ERNTS NGSGSEDQVD PRLIDGK UniProtKB: Glucagon receptor |
-分子 #6: Glucagon
分子 | 名称: Glucagon / 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: 3.486781 KDa |
配列 | 文字列: HSQGTFTSDY SKYLDSRRAQ DFVQWLMNT UniProtKB: Pro-glucagon |
-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: 7.5 |
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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 K2 SUMMIT (4k x 4k) 平均電子線量: 1.875 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD |
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: |
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最終 再構成 | 想定した対称性 - 点群: C1 (非対称) / 解像度のタイプ: BY AUTHOR / 解像度: 3.7 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 169878 |
初期 角度割当 | タイプ: ANGULAR RECONSTITUTION |
最終 角度割当 | タイプ: ANGULAR RECONSTITUTION |