+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7ki0 | ||||||||||||||||||
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タイトル | Semaglutide-bound Glucagon-Like Peptide-1 (GLP-1) Receptor in Complex with Gs protein | ||||||||||||||||||
要素 |
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キーワード | MEMBRANE PROTEIN / Glucagon-Like peptide-1 (GLP-1) Receptor semaglutide cryoEM | ||||||||||||||||||
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 / response to psychosocial stress / regulation of heart contraction / peptide hormone binding / PKA activation in glucagon signalling / 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 / response to psychosocial stress / regulation of heart contraction / peptide hormone binding / PKA activation in glucagon signalling / hair follicle placode formation / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / developmental growth / D1 dopamine receptor binding / intracellular transport / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / beta-2 adrenergic receptor binding / adenylate cyclase activator activity / negative regulation of blood pressure / cAMP-mediated signaling / trans-Golgi network membrane / insulin-like growth factor receptor binding / ionotropic glutamate receptor binding / G-protein beta/gamma-subunit complex binding / bone development / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine 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 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / cognition / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / platelet aggregation / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / transmembrane signaling receptor activity / GPER1 signaling / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / sensory perception of smell / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / positive regulation of cold-induced thermogenesis / 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 / 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 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.5 Å | ||||||||||||||||||
データ登録者 | Zhang, X. / Belousoff, M.J. / Danev, R. / Sexton, P.M. / Wootten, D. | ||||||||||||||||||
資金援助 | オーストラリア, 日本, 5件
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引用 | ジャーナル: Cell Rep / 年: 2021 タイトル: Structure and dynamics of semaglutide- and taspoglutide-bound GLP-1R-Gs complexes. 著者: Xin Zhang / Matthew J Belousoff / Yi-Lynn Liang / Radostin Danev / Patrick M Sexton / Denise Wootten / 要旨: The glucagon-like peptide-1 receptor (GLP-1R) regulates insulin secretion, carbohydrate metabolism, and appetite and is an important target for treatment of type 2 diabetes and obesity. Multiple GLP- ...The glucagon-like peptide-1 receptor (GLP-1R) regulates insulin secretion, carbohydrate metabolism, and appetite and is an important target for treatment of type 2 diabetes and obesity. Multiple GLP-1R agonists have entered into clinical trials, with some, such as semaglutide, progressing to approval. Others, including taspoglutide, failed due to the high incidence of side effects or insufficient efficacy. GLP-1R agonists have a broad spectrum of signaling profiles, but molecular understanding is limited by a lack of structural information on how different agonists engage with the GLP-1R. Here, we report cryoelectron microscopy (cryo-EM) structures and cryo-EM 3D variability analysis of semaglutide- and taspoglutide-bound GLP-1R-Gs protein complexes. These reveal similar peptide interactions to GLP-1 but different motions within the receptor and bound peptides, providing insights into the molecular determinants of GLP-1R peptide engagement. | ||||||||||||||||||
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 | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7ki0.cif.gz | 218.2 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7ki0.ent.gz | 174.8 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7ki0.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/ki/7ki0 ftp://data.pdbj.org/pub/pdb/validation_reports/ki/7ki0 | HTTPS FTP |
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-関連構造データ
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
-Guanine nucleotide-binding protein ... , 3種, 3分子 ABG
#1: タンパク質 | 分子量: 45699.434 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNAS, GNAS1, GSP / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: P63092 |
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#2: タンパク質 | 分子量: 37413.863 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNB1 / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: P62873 |
#3: タンパク質 | 分子量: 6375.332 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNG2 / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: P59768 |
-抗体 / タンパク質・ペプチド / タンパク質 , 3種, 3分子 NPR
#4: 抗体 | 分子量: 13885.439 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Lama glama (ラマ) / 発現宿主: Escherichia coli (大腸菌) |
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#5: タンパク質・ペプチド | 分子量: 3401.740 Da / 分子数: 1 / 由来タイプ: 合成 / 由来: (合成) synthetic construct (人工物) |
#6: タンパク質 | 分子量: 56748.418 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GLP1R / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: P43220 |
-非ポリマー , 2種, 80分子
#7: 化合物 | ChemComp-WF1 / |
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#8: 水 | ChemComp-HOH / |
-詳細
研究の焦点であるリガンドがあるか | N |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-試料調製
構成要素 | 名称: Semaglutide-GLP-1R-Gs complex / タイプ: COMPLEX / Entity ID: #1-#6 / 由来: RECOMBINANT |
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分子量 | 実験値: NO |
由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Trichoplusia ni (イラクサキンウワバ) |
緩衝液 | pH: 7.4 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 平均露光時間: 2.996 sec. / 電子線照射量: 0.887 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.18.2_3874: / 分類: 精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 2.5 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 886738 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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