+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-24680 | ||||||||||||||||||||||||
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タイトル | Peptide-19 bound to the Glucagon-Like Peptide-1 Receptor (GLP-1R) | ||||||||||||||||||||||||
マップデータ | The sharpened cryoSPARC consensus map at 2.14A. | ||||||||||||||||||||||||
試料 |
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機能・相同性 | 機能・相同性情報 glucagon-like peptide 1 receptor activity / glucagon receptor activity / hormone secretion / positive regulation of blood pressure / post-translational protein targeting to membrane, translocation / regulation of heart contraction / response to psychosocial stress / PKA activation in glucagon signalling / peptide hormone binding / hair follicle placode formation ...glucagon-like peptide 1 receptor activity / glucagon receptor activity / hormone secretion / positive regulation of blood pressure / post-translational protein targeting to membrane, translocation / regulation of heart contraction / response to psychosocial stress / PKA activation in glucagon signalling / peptide hormone binding / hair follicle placode formation / developmental growth / D1 dopamine receptor binding / intracellular transport / renal water homeostasis / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / cellular response to glucagon stimulus / cAMP-mediated signaling / negative regulation of blood pressure / adenylate cyclase activator activity / regulation of insulin secretion / trans-Golgi network membrane / negative regulation of inflammatory response to antigenic stimulus / bone development / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / G protein activity / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / platelet aggregation / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / cognition / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / 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 / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / 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 / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / transmembrane signaling receptor activity / heterotrimeric G-protein complex / sensory perception of smell / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / positive regulation of cold-induced thermogenesis / retina development in camera-type eye / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) 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 / G alpha (q) signalling events / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / learning or memory / cell surface receptor signaling pathway / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / protein-containing complex binding / GTP binding / signal transduction / extracellular exosome / membrane / metal ion binding / plasma membrane / cytosol / cytoplasm 類似検索 - 分子機能 | ||||||||||||||||||||||||
生物種 | Homo sapiens (ヒト) / Lama glama (ラマ) / 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: 2.14 Å | ||||||||||||||||||||||||
データ登録者 | Johnson RM / Danev R / Sexton PM / Wootten D | ||||||||||||||||||||||||
資金援助 | 日本, 7件
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引用 | ジャーナル: Biochem Biophys Res Commun / 年: 2021 タイトル: Cryo-EM structure of the dual incretin receptor agonist, peptide-19, in complex with the glucagon-like peptide-1 receptor. 著者: Rachel M Johnson / Xin Zhang / Sarah J Piper / Theodore J Nettleton / Teresa H Vandekolk / Christopher J Langmead / Radostin Danev / Patrick M Sexton / Denise Wootten / 要旨: Dual agonists that can activate both the glucagon-like peptide-1 receptor (GLP-1R) and the gastric inhibitory polypeptide receptor (GIPR) have demonstrated high efficacy for the treatment of ...Dual agonists that can activate both the glucagon-like peptide-1 receptor (GLP-1R) and the gastric inhibitory polypeptide receptor (GIPR) have demonstrated high efficacy for the treatment of metabolic disease. Peptide-19 is a prototypical dual agonist that has high potency at both GLP-1R and GIPR but has a distinct signalling profile relative to the native peptides at the cognate receptors. In this study, we solved the structure of peptide-19 bound to the GLP-1R in complex with Gs protein, and compared the structure and dynamics of this complex to that of published structures of GLP-1R:Gs in complex with other receptor agonists. Unlike other peptide-bound receptor complexes, peptide-19:GLP-1R:Gs demonstrated a more open binding pocket where transmembrane domain (TM) 6, TM7 and the interconnecting extracellular loop 3 (ECL3) were located away from the peptide, with no interactions between peptide-19 and TM6/ECL3. Analysis of conformational variance of the complex revealed that peptide-19 was highly dynamic and underwent binding and unbinding motions facilitated by the more open TM binding pocket. Both the consensus structure of the GLP-1R complex with peptide-19 and the dynamics of this complex were distinct from previously described GLP-1R structures providing unique insights into the mode of GLP-1R activation by this dual agonist. | ||||||||||||||||||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | EMマップ: SurfViewMolmilJmol/JSmol |
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_24680.map.gz | 117.8 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-24680-v30.xml emd-24680.xml | 44.1 KB 44.1 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_24680_fsc.xml | 11.1 KB | 表示 | FSCデータファイル |
画像 | emd_24680.png | 41.4 KB | ||
マスクデータ | emd_24680_msk_1.map | 125 MB | マスクマップ | |
その他 | emd_24680_additional_1.map.gz emd_24680_additional_10.map.gz emd_24680_additional_2.map.gz emd_24680_additional_3.map.gz emd_24680_additional_4.map.gz emd_24680_additional_5.map.gz emd_24680_additional_6.map.gz emd_24680_additional_7.map.gz emd_24680_additional_8.map.gz emd_24680_additional_9.map.gz emd_24680_half_map_1.map.gz emd_24680_half_map_2.map.gz | 61.5 MB 84.4 MB 108.3 MB 7.2 MB 10.8 MB 111 MB 110.9 MB 82.6 MB 82.8 MB 79.9 MB 116 MB 116 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-24680 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-24680 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_24680_validation.pdf.gz | 745.9 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_24680_full_validation.pdf.gz | 745.4 KB | 表示 | |
XML形式データ | emd_24680_validation.xml.gz | 19.1 KB | 表示 | |
CIF形式データ | emd_24680_validation.cif.gz | 24.6 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24680 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24680 | HTTPS FTP |
-関連構造データ
-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_24680.map.gz / 形式: CCP4 / 大きさ: 125 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | The sharpened cryoSPARC consensus map at 2.14A. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: 0.65 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
+追加マップ: The unsharpened cryoSPARC consensus map.
+追加マップ: The local resolution map for the ECD-focussed refinement...
+追加マップ: Unsharpened receptor-only focussed refinement from RELION
+追加マップ: Sharpened receptor-only focussed refinement from RELION
+追加マップ: Sharpened consensus refinement generated in RELION
+追加マップ: Unsharpened ECD-only focussed refinement from RELION
+追加マップ: Unsharpened consensus refinement generated in RELION
+追加マップ: The local resolution map for the receptor-focussed refinement...
+追加マップ: The local resolution map for the consensus map generated using RELION
+追加マップ: The local resolution map for the best-resolved ECD...
+ハーフマップ: Half map B from cryoSPARC consensus refinement.
+ハーフマップ: Half map A from cryoSPARC consensus refinement.
-試料の構成要素
-全体 : Peptide-19-GLP-1R-Gs complex
全体 | 名称: Peptide-19-GLP-1R-Gs complex |
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要素 |
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-超分子 #1: Peptide-19-GLP-1R-Gs complex
超分子 | 名称: Peptide-19-GLP-1R-Gs complex / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#6 |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
-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: Homo sapiens (ヒト) |
分子量 | 理論値: 45.683434 KDa |
組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
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 |
-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: 37.285734 KDa |
組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
配列 | 文字列: SELDQLRQEA EQLKNQIRDA RKACADATLS QITNNIDPVG RIQMRTRRTL RGHLAKIYAM HWGTDSRLLV SASQDGKLII WDSYTTNKV HAIPLRSSWV MTCAYAPSGN YVACGGLDNI CSIYNLKTRE GNVRVSRELA GHTGYLSCCR FLDDNQIVTS S GDTTCALW ...文字列: SELDQLRQEA EQLKNQIRDA RKACADATLS QITNNIDPVG RIQMRTRRTL RGHLAKIYAM HWGTDSRLLV SASQDGKLII WDSYTTNKV HAIPLRSSWV MTCAYAPSGN YVACGGLDNI CSIYNLKTRE GNVRVSRELA GHTGYLSCCR FLDDNQIVTS S GDTTCALW DIETGQQTTT FTGHTGDVMS LSLAPDTRLF VSGACDASAK LWDVREGMCR QTFTGHESDI NAICFFPNGN AF ATGSDDA TCRLFDLRAD QELMTYSHDN IICGITSVSF SKSGRLLLAG YDDFNCNVWD ALKADRAGVL AGHDNRVSCL GVT DDGMAV ATGSWDSFLK IWN |
-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: 6.375332 KDa |
組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
配列 | 文字列: NTASIAQARK LVEQLKMEAN IDRIKVSKAA ADLMAYCEAH AKEDPLLTPV PASENPFR |
-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: Lama glama (ラマ) |
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 |
-分子 #5: Glucagon-like peptide 1 receptor
分子 | 名称: Glucagon-like peptide 1 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: Homo sapiens (ヒト) |
分子量 | 理論値: 56.668316 KDa |
組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
配列 | 文字列: MKTIIALSYI FCLVFADYKD DDDLEVLFQG PRPQGATVSL WETVQKWREY RRQCQRSLTE DPPPATDLFC NRTFDEYACW PDGEPGSFV NVSCPWYLPW ASSVPQGHVY RFCTAEGLWL QKDNSSLPWR DLSECEESKR GERSSPEEQL LFLYIIYTVG Y ALSFSALV ...文字列: MKTIIALSYI FCLVFADYKD DDDLEVLFQG PRPQGATVSL WETVQKWREY RRQCQRSLTE DPPPATDLFC NRTFDEYACW PDGEPGSFV NVSCPWYLPW ASSVPQGHVY RFCTAEGLWL QKDNSSLPWR DLSECEESKR GERSSPEEQL LFLYIIYTVG Y ALSFSALV IASAILLGFR HLHCTRNYIH LNLFASFILR ALSVFIKDAA LKWMYSTAAQ QHQWDGLLSY QDSLSCRLVF LL MQYCVAA NYYWLLVEGV YLYTLLAFSV FSEQWIFRLY VSIGWGVPLL FVVPWGIVKY LYEDEGCWTR NSNMNYWLII RLP ILFAIG VNFLIFVRVI CIVVSKLKAN LMCKTDIKCR LAKSTLTLIP LLGTHEVIFA FVMDEHARGT LRHIKLFTEL SFTS FQGLM VAILYCFVNN EVQLEFRKSW ERWRLEHLHI QRDSSMKPLK CPTSSLSSGA TAGSSMYTAT CQASCSPAGL EVLFQ GPHH HHHHHH |
-分子 #6: Peptide-19
分子 | 名称: Peptide-19 / 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: synthetic construct (人工物) |
分子量 | 理論値: 4.093503 KDa |
配列 | 文字列: Y(AIB)EGTFTSDY SIYLDKQAA(AIB) EFVNWLLAGG PSAPPPSK |
-分子 #7: water
分子 | 名称: water / タイプ: ligand / ID: 7 / コピー数: 1 / 式: HOH |
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分子量 | 理論値: 18.015 Da |
Chemical component information | ChemComp-HOH: |
-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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グリッド | モデル: UltrAuFoil R1.2/1.3 / 材質: GOLD / メッシュ: 300 |
凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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特殊光学系 | エネルギーフィルター - 名称: GIF Bioquantum / エネルギーフィルター - スリット幅: 15 eV |
撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 撮影したグリッド数: 1 / 実像数: 6858 / 平均露光時間: 4.352 sec. / 平均電子線量: 70.15 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 / Cs: 2.7 mm / 倍率(公称値): 130000 |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |