登録情報 データベース : EMDB / ID : EMD-20278 構造の表示 ダウンロードとリンクタイトル PAC1 GPCR Receptor complex マップデータpost-processed map 詳細 試料複合体 : Complex of active-state Pituitary adenylate cyclase-activating polypeptide type I receptor with heterotrimeric Gs protein.複合体 : 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, Pituitary adenylate cyclase-activating polypeptide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タンパク質・ペプチド : Pituitary adenylate cyclase-activating polypeptide複合体 : Nanobody 35複合体 : Pituitary adenylate cyclase-activating polypeptide type I receptorタンパク質・ペプチド : Pituitary adenylate cyclase-activating polypeptide type I receptor 詳細 キーワード GPCR / MEMBRANE 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
negative regulation of response to reactive oxygen species / pituitary adenylate cyclase activating polypeptide activity / development of primary female sexual characteristics / type 1 vasoactive intestinal polypeptide receptor binding / type 2 vasoactive intestinal polypeptide receptor binding / pituitary adenylate cyclase-activating polypeptide receptor activity / vasoactive intestinal polypeptide receptor activity / positive regulation of growth hormone secretion / positive regulation of chemokine (C-C motif) ligand 5 production / NGF-independant TRKA activation ... negative regulation of response to reactive oxygen species / pituitary adenylate cyclase activating polypeptide activity / development of primary female sexual characteristics / type 1 vasoactive intestinal polypeptide receptor binding / type 2 vasoactive intestinal polypeptide receptor binding / pituitary adenylate cyclase-activating polypeptide receptor activity / vasoactive intestinal polypeptide receptor activity / positive regulation of growth hormone secretion / positive regulation of chemokine (C-C motif) ligand 5 production / NGF-independant TRKA activation / positive regulation of small GTPase mediated signal transduction / neuropeptide hormone activity / regulation of G protein-coupled receptor signaling pathway / G protein-coupled peptide receptor activity / positive regulation of protein kinase activity / neuropeptide binding / insulin secretion / peptide hormone receptor binding / positive regulation of inositol phosphate biosynthetic process / adenylate cyclase-activating G protein-coupled bile acid receptor signaling pathway / adenylate cyclase-activating serotonin receptor signaling pathway / negative regulation of cell cycle / positive regulation of cAMP/PKA signal transduction / peptide hormone binding / regulation of skeletal muscle contraction / positive regulation of GTPase activity / adenylate cyclase binding / positive regulation of calcium ion transport into cytosol / PKA activation in glucagon signalling / hair follicle placode formation / developmental growth / bicellular tight junction / intracellular transport / cAMP/PKA signal transduction / multicellular organismal response to stress / D1 dopamine receptor binding / vascular endothelial cell response to laminar fluid shear stress / renal water homeostasis / activation of adenylate cyclase activity / Hedgehog 'off' state / cellular response to acidic pH / adenylate cyclase-activating adrenergic receptor signaling pathway / cellular response to glucagon stimulus / intracellular glucose homeostasis / positive regulation of insulin secretion involved in cellular response to glucose stimulus / adenylate cyclase activator activity / trans-Golgi network membrane / neuropeptide signaling pathway / negative regulation of inflammatory response to antigenic stimulus / female pregnancy / response to prostaglandin E / bone development / caveola / platelet aggregation / cognition / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / small GTPase binding / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / neuron projection development / G protein-coupled acetylcholine receptor signaling pathway / positive regulation of insulin secretion / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / 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) / sensory perception of smell / photoreceptor disc membrane / ADP signalling through P2Y purinoceptor 12 / 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 / response to estradiol / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / cell-cell signaling / 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 / regulation of protein localization / GPER1 signaling / cellular response to prostaglandin E stimulus / heterotrimeric G-protein complex / G alpha (12/13) signalling events / positive regulation of cold-induced thermogenesis / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / extracellular vesicle 類似検索 - 分子機能 GPCR, family 2, pituitary adenylate cyclase activating polypeptide type 1 receptor / : / 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, pituitary adenylate cyclase activating polypeptide type 1 receptor / : / 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 / G-protein coupled receptors family 2 signature 2. / 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 / G protein alpha subunit, helical insertion / G protein alpha subunit / Guanine nucleotide binding protein (G-protein), alpha subunit / G-protein alpha subunit / G-alpha domain profile. / 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 Pituitary adenylate cyclase-activating polypeptide / Pituitary adenylate cyclase-activating polypeptide type I receptor / Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Guanine nucleotide-binding protein G(s) subunit alpha isoforms short 類似検索 - 構成要素生物種 Homo sapiens (ヒト) / Lama glama (ラマ)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.01 Å 詳細 データ登録者Belousoff MJ / Liang YL 資金援助 オーストラリア, 日本, 9件 詳細 詳細を隠すOrganization Grant number 国 National Health and Medical Research Council (Australia) 1065410 オーストラリア National Health and Medical Research Council (Australia) 1061044 オーストラリア National Health and Medical Research Council (Australia) 1120919 オーストラリア National Health and Medical Research Council (Australia) 1126857 オーストラリア National Health and Medical Research Council (Australia) 1055134 オーストラリア National Health and Medical Research Council (Australia) 1159006 オーストラリア National Health and Medical Research Council (Australia) 1150083 オーストラリア Japan Society for the Promotion of Science KAKENHI #18H06043 日本 Japan Society for the Promotion of Science PRESTO #18069571 日本
引用ジャーナル : Mol Cell / 年 : 2020タイトル : Toward a Structural Understanding of Class B GPCR Peptide Binding and Activation.著者: Yi-Lynn Liang / Matthew J Belousoff / Peishen Zhao / Cassandra Koole / Madeleine M Fletcher / Tin T Truong / Villy Julita / George Christopoulos / H Eric Xu / Yan Zhang / Maryam Khoshouei / ... 著者 : Yi-Lynn Liang / Matthew J Belousoff / Peishen Zhao / Cassandra Koole / Madeleine M Fletcher / Tin T Truong / Villy Julita / George Christopoulos / H Eric Xu / Yan Zhang / Maryam Khoshouei / Arthur Christopoulos / Radostin Danev / Patrick M Sexton / Denise Wootten / 要旨 : Class B G protein-coupled receptors (GPCRs) are important therapeutic targets for major diseases. Here, we present structures of peptide and Gs-bound pituitary adenylate cyclase-activating peptide, ... Class B G protein-coupled receptors (GPCRs) are important therapeutic targets for major diseases. Here, we present structures of peptide and Gs-bound pituitary adenylate cyclase-activating peptide, PAC1 receptor, and corticotropin-releasing factor (CRF), (CRF1) receptor. Together with recently solved structures, these provide coverage of the major class B GPCR subfamilies. Diverse orientations of the extracellular domain to the receptor core in different receptors are at least partially dependent on evolutionary conservation in the structure and nature of peptide interactions. Differences in peptide interactions to the receptor core also influence the interlinked TM2-TM1-TM6/ECL3/TM7 domain, and this is likely important in their diverse signaling. However, common conformational reorganization of ECL2, linked to reorganization of ICL2, modulates G protein contacts. Comparison between receptors reveals ICL2 as a key domain forming dynamic G protein interactions in a receptor- and ligand-specific manner. This work advances our understanding of class B GPCR activation and Gs coupling. 履歴 登録 2019年6月10日 - ヘッダ(付随情報) 公開 2019年7月3日 - マップ公開 2020年2月5日 - 更新 2024年10月16日 - 現状 2024年10月16日 処理サイト : RCSB / 状態 : 公開
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