+
データを開く
-
基本情報
| 登録情報 | データベース: EMDB / ID: EMD-24680 | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 |
| ||||||||||||||||||||||||
キーワード | Glucagon-Like peptide-1 Receptor (GLP-1R) / Peptide-19 cryo-EM / MEMBRANE PROTEIN | ||||||||||||||||||||||||
| 機能・相同性 | 機能・相同性情報glucagon-like peptide 1 receptor activity / glucagon receptor activity / positive regulation of blood pressure / hormone secretion / post-translational protein targeting to membrane, translocation / response to psychosocial stress / regulation of heart contraction / adenylate cyclase-activating G protein-coupled bile acid receptor signaling pathway / adenylate cyclase-activating serotonin receptor signaling pathway / peptide hormone binding ...glucagon-like peptide 1 receptor activity / glucagon receptor activity / positive regulation of blood pressure / hormone secretion / post-translational protein targeting to membrane, translocation / response to psychosocial stress / regulation of heart contraction / adenylate cyclase-activating G protein-coupled bile acid receptor signaling pathway / adenylate cyclase-activating serotonin receptor signaling pathway / peptide hormone binding / regulation of skeletal muscle contraction / PKA activation in glucagon signalling / hair follicle placode formation / developmental growth / intracellular transport / D1 dopamine receptor binding / vascular endothelial cell response to laminar fluid shear stress / renal water homeostasis / activation of adenylate cyclase activity / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway / cellular response to acidic pH / negative regulation of blood pressure / cellular response to glucagon stimulus / intracellular glucose homeostasis / adenylate cyclase activator activity / positive regulation of insulin secretion involved in cellular response to glucose stimulus / trans-Golgi network membrane / negative regulation of inflammatory response to antigenic stimulus / response to prostaglandin E / bone development / platelet aggregation / cognition / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G protein-coupled acetylcholine receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / positive regulation of insulin secretion / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / ADP signalling through P2Y purinoceptor 12 / sensory perception of smell / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / transmembrane signaling receptor activity / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / ADORA2B mediated anti-inflammatory cytokines production / 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 / heterotrimeric G-protein complex / G-protein beta-subunit binding / G alpha (12/13) signalling events / Inactivation, recovery and regulation of the phototransduction cascade / positive regulation of cold-induced thermogenesis / extracellular vesicle / sensory perception of taste / adenylate cyclase-activating G protein-coupled receptor signaling pathway / Thrombin signalling through proteinase activated receptors (PARs) / signaling receptor complex adaptor activity / positive regulation of cytosolic calcium ion concentration / retina development in camera-type eye / GTPase binding / G protein activity / fibroblast proliferation / Ca2+ pathway / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) 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 / Ras protein signal transduction / learning or memory / cell surface receptor signaling pathway / cell population proliferation / Extra-nuclear estrogen signaling / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / GTP binding / protein-containing complex binding 類似検索 - 分子機能 | ||||||||||||||||||||||||
| 生物種 | Homo sapiens (ヒト) / ![]() | ||||||||||||||||||||||||
| 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 | ||||||||||||||||||||||||
| 資金援助 | 日本, 7件
| ||||||||||||||||||||||||
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 |
|
-
構造の表示
| ムービー |
ムービービューア |
|---|---|
| 構造ビューア | EMマップ: SurfView Molmil Jmol/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 | |
|---|---|---|---|---|
| ヘッダ (付随情報) | emd-24680-v30.xml emd-24680.xml | 50.7 KB 50.7 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 | |
| Filedesc metadata | emd-24680.cif.gz | 8.4 KB | ||
| 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 |
-関連構造データ
-
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_24680.map.gz / 形式: CCP4 / 大きさ: 125 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
-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 |
|---|---|
| 要素 |
|
-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 |
|---|---|
| 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 |
|---|---|
| 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 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 |
|---|---|
| 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 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 |
|---|---|
| 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 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 |
|---|---|
| 由来(天然) | 生物種: ![]() |
| 分子量 | 理論値: 13.885439 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 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 |
|---|---|
| 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 UniProtKB: Glucagon-like peptide 1 receptor |
-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 |
|---|---|
| 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 |
|---|---|
| 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 |
|---|---|
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 |
|---|---|
| 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 |
|---|---|
| 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 |
ムービー
コントローラー
万見について



キーワード
Homo sapiens (ヒト)
データ登録者
日本, 7件
引用
UCSF Chimera





























Z (Sec.)
Y (Row.)
X (Col.)





























































































































Trichoplusia ni (イラクサキンウワバ)

解析


