登録情報 データベース : EMDB / ID : EMD-30590 構造の表示 ダウンロードとリンクタイトル Cryo-EM structure of the human glucagon-like peptide-2 receptor-Gs protein complex マップデータ 詳細 試料複合体 : Cryo-EM structure of the human glucagon-like peptide-2 receptor-Gs protein complex複合体 : Guanine nucleotide-binding proteinタンパク質・ペプチド : Guanine nucleotide-binding protein G(s) subunit alpha isoforms shortタンパク質・ペプチド : Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1タンパク質・ペプチド : Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2複合体 : Nanobody-35複合体 : Glucagon-like peptide 2 receptorタンパク質・ペプチド : Pro-glucagonタンパク質・ペプチド : Glucagon-like peptide 2 receptorリガンド : water 詳細 キーワード Glucagon-like peptide-2 receptor / Drug target / Class B GPCR / BIOSYNTHETIC PROTEIN機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
glucagon receptor binding / Olfactory Signaling Pathway / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / glucagon receptor activity / sensory perception of chemical stimulus / protein kinase A signaling / mu-type opioid receptor binding / Activation of the phototransduction cascade / corticotropin-releasing hormone receptor 1 binding ... glucagon receptor binding / Olfactory Signaling Pathway / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / glucagon receptor activity / sensory perception of chemical stimulus / protein kinase A signaling / mu-type opioid receptor binding / Activation of the phototransduction cascade / corticotropin-releasing hormone receptor 1 binding / negative regulation of execution phase of apoptosis / feeding behavior / beta-2 adrenergic receptor binding / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G alpha (12/13) signalling events / Glucagon-type ligand receptors / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Adrenaline,noradrenaline inhibits insulin secretion / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Ca2+ pathway / Thrombin signalling through proteinase activated receptors (PARs) / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / G alpha (q) signalling events / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / Vasopressin regulates renal water homeostasis via Aquaporins / positive regulation of calcium ion import / peptide hormone binding / Synthesis, secretion, and deacylation of Ghrelin / D1 dopamine receptor binding / positive regulation of insulin secretion involved in cellular response to glucose stimulus / adenylate cyclase-activating adrenergic receptor signaling pathway / insulin-like growth factor receptor binding / positive regulation of gluconeogenesis / ionotropic glutamate receptor binding / cellular response to glucagon stimulus / regulation of insulin secretion / adenylate cyclase activator activity / response to activity / gluconeogenesis / G protein-coupled receptor activity / hormone activity / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / adenylate cyclase-activating G protein-coupled receptor signaling pathway / Glucagon signaling in metabolic regulation / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / Glucagon-type ligand receptors / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / cellular response to catecholamine stimulus / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / glucose homeostasis / G-protein beta-subunit binding / heterotrimeric G-protein complex / sensory perception of taste / signaling receptor complex adaptor activity / retina development in camera-type eye / GTPase binding / secretory granule lumen / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / 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 / cell surface receptor signaling pathway / cell population proliferation / positive regulation of ERK1 and ERK2 cascade / G protein-coupled receptor signaling pathway / receptor ligand activity / endoplasmic reticulum lumen / signaling receptor binding / GTPase activity / positive regulation of cell population proliferation / synapse / negative regulation of apoptotic process / protein-containing complex binding / GTP binding / extracellular space / extracellular region / metal ion binding / identical protein binding / membrane / plasma membrane / cytoplasm 類似検索 - 分子機能 GPCR family 2, glucagon-like peptide 2 receptor / Glucagon / Glucagon/GIP/secretin/VIP / Peptide hormone / Glucagon / GIP / secretin / VIP family signature. / Glucagon like hormones / G-protein coupled receptors family 2 signature 1. / : / GPCR, family 2, extracellular hormone receptor domain / G-protein coupled receptors family 2 profile 1. ... GPCR family 2, glucagon-like peptide 2 receptor / Glucagon / Glucagon/GIP/secretin/VIP / Peptide hormone / Glucagon / GIP / secretin / VIP family signature. / Glucagon like hormones / G-protein coupled receptors family 2 signature 1. / : / GPCR, family 2, extracellular hormone receptor domain / G-protein coupled receptors family 2 profile 1. / Domain present in hormone receptors / Hormone receptor domain / GPCR family 2, extracellular hormone receptor domain superfamily / GPCR, family 2, secretin-like, conserved site / GPCR, family 2, secretin-like / 7 transmembrane receptor (Secretin family) / GPCR, family 2-like / G-protein coupled receptors family 2 profile 2. / G-protein alpha subunit, group S / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G-alpha domain profile. / G protein alpha subunit / G-protein, gamma subunit / G-protein gamma subunit domain profile. / G-protein gamma-like domain / G-protein gamma-like domain superfamily / GGL domain / G protein gamma subunit-like motifs / GGL domain / G protein beta WD-40 repeat protein / Guanine nucleotide-binding protein, beta subunit / G-protein, beta subunit / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性 Glucagon-like peptide 2 receptor / Pro-glucagon / Guanine nucleotide-binding protein G(s) subunit alpha isoforms short / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 類似検索 - 構成要素生物種 Bos taurus (ウシ) / synthetic construct (人工物) / 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 : 3.0 Å 詳細 データ登録者Sun W / Chen L 引用ジャーナル : Cell Res / 年 : 2020タイトル : A unique hormonal recognition feature of the human glucagon-like peptide-2 receptor.著者: Wen Sun / Li-Nan Chen / Qingtong Zhou / Li-Hua Zhao / Dehua Yang / Huibing Zhang / Zhaotong Cong / Dan-Dan Shen / Fenghui Zhao / Fulai Zhou / Xiaoqing Cai / Yan Chen / Yan Zhou / Sarina ... 著者 : Wen Sun / Li-Nan Chen / Qingtong Zhou / Li-Hua Zhao / Dehua Yang / Huibing Zhang / Zhaotong Cong / Dan-Dan Shen / Fenghui Zhao / Fulai Zhou / Xiaoqing Cai / Yan Chen / Yan Zhou / Sarina Gadgaard / Wijnand J C van der Velden / Suwen Zhao / Yi Jiang / Mette M Rosenkilde / H Eric Xu / Yan Zhang / Ming-Wei Wang / 要旨 : Glucagon-like peptides (GLP-1 and GLP-2) are two proglucagon-derived intestinal hormones that mediate distinct physiological functions through two related receptors (GLP-1R and GLP-2R) which are ... Glucagon-like peptides (GLP-1 and GLP-2) are two proglucagon-derived intestinal hormones that mediate distinct physiological functions through two related receptors (GLP-1R and GLP-2R) which are important drug targets for metabolic disorders and Crohn's disease, respectively. Despite great progress in GLP-1R structure determination, our understanding on the differences of peptide binding and signal transduction between these two receptors remains elusive. Here we report the electron microscopy structure of the human GLP-2R in complex with GLP-2 and a G heterotrimer. To accommodate GLP-2 rather than GLP-1, GLP-2R fine-tunes the conformations of the extracellular parts of transmembrane helices (TMs) 1, 5, 7 and extracellular loop 1 (ECL1). In contrast to GLP-1, the N-terminal histidine of GLP-2 penetrates into the receptor core with a unique orientation. The middle region of GLP-2 engages with TM1 and TM7 more extensively than with ECL2, and the GLP-2 C-terminus closely attaches to ECL1, which is the most protruded among 9 class B G protein-coupled receptors (GPCRs). Functional studies revealed that the above three segments of GLP-2 are essential for GLP-2 recognition and receptor activation, especially the middle region. These results provide new insights into the molecular basis of ligand specificity in class B GPCRs and may facilitate the development of more specific therapeutics. 履歴 登録 2020年9月29日 - ヘッダ(付随情報) 公開 2020年12月16日 - マップ公開 2020年12月16日 - 更新 2025年7月2日 - 現状 2025年7月2日 処理サイト : PDBj / 状態 : 公開
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