登録情報 データベース : EMDB / ID : EMD-20277 構造の表示 ダウンロードとリンクタイトル CRF1 Receptor Gs GPCR protein complex with CRF1 peptide. マップデータPost-processed map 詳細 試料複合体 : Complex of active-state Corticotropin-releasing hormone receptor 1 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, Corticotropin-releasing factor receptor 1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 : Corticotropin-releasing factor receptor 1複合体 : Nanobody 35複合体 : Corticoliberinタンパク質・ペプチド : Corticoliberinリガンド : water 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
corticotropin-releasing hormone activity / positive regulation of digestive system process / diterpenoid metabolic process / corticotropin-releasing hormone binding / positive regulation of circadian sleep/wake cycle, wakefulness / negative regulation of circadian sleep/wake cycle, REM sleep / corticotropin-releasing hormone receptor activity / regulation of corticosterone secretion / corticotrophin-releasing factor receptor activity / corticotropin-releasing hormone receptor 2 binding ... corticotropin-releasing hormone activity / positive regulation of digestive system process / diterpenoid metabolic process / corticotropin-releasing hormone binding / positive regulation of circadian sleep/wake cycle, wakefulness / negative regulation of circadian sleep/wake cycle, REM sleep / corticotropin-releasing hormone receptor activity / regulation of corticosterone secretion / corticotrophin-releasing factor receptor activity / corticotropin-releasing hormone receptor 2 binding / corticotropin secretion / positive regulation of corticosterone secretion / positive regulation of cortisol secretion / positive regulation of corticotropin secretion / negative regulation of glucagon secretion / positive regulation of behavioral fear response / general adaptation syndrome, behavioral process / glucocorticoid biosynthetic process / cellular response to corticotropin-releasing hormone stimulus / varicosity / MECP2 regulates transcription of neuronal ligands / negative regulation of luteinizing hormone secretion / parturition / monoatomic ion homeostasis / regulation of serotonin secretion / hormone-mediated apoptotic signaling pathway / negative regulation of norepinephrine secretion / negative regulation of voltage-gated calcium channel activity / neuronal dense core vesicle lumen / negative regulation of epinephrine secretion / response to ether / behavioral response to ethanol / neuropeptide hormone activity / fear response / synaptic transmission, dopaminergic / corticotropin-releasing hormone receptor 1 binding / response to aldosterone / negative regulation of systemic arterial blood pressure / regulation of NMDA receptor activity / Class B/2 (Secretin family receptors) / G protein-coupled peptide receptor activity / cellular response to cocaine / adrenal gland development / response to corticosterone / response to pain / positive regulation of calcium ion import / hypothalamus development / exploration behavior / response to immobilization stress / positive regulation of cAMP/PKA signal transduction / locomotory exploration behavior / associative learning / PKA activation in glucagon signalling / developmental growth / hair follicle placode formation / cellular response to dexamethasone stimulus / D1 dopamine receptor binding / intracellular transport / positive regulation of insulin secretion involved in cellular response to glucose stimulus / 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 glucagon stimulus / regulation of insulin secretion / lung development / adenylate cyclase activator activity / trans-Golgi network membrane / negative regulation of inflammatory response to antigenic stimulus / female pregnancy / postsynaptic density membrane / hormone activity / bone development / G protein-coupled receptor activity / response to estrogen / platelet aggregation / cognition / G-protein beta/gamma-subunit complex binding / adenylate cyclase-activating G protein-coupled receptor signaling pathway / long-term synaptic potentiation / 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 / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / photoreceptor disc membrane / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion 類似検索 - 分子機能 GPCR, family 2, corticotropin releasing factor receptor, type 1 / Urocortin/corticotropin-releasing factor / Corticotropin-releasing factor conserved site / Corticotropin-releasing factor family signature. / corticotropin-releasing factor / Corticotropin-releasing factor / GPCR, family 2, corticotropin releasing factor receptor / Corticotropin-releasing factor family / G-protein coupled receptors family 2 signature 1. / : ... GPCR, family 2, corticotropin releasing factor receptor, type 1 / Urocortin/corticotropin-releasing factor / Corticotropin-releasing factor conserved site / Corticotropin-releasing factor family signature. / corticotropin-releasing factor / Corticotropin-releasing factor / GPCR, family 2, corticotropin releasing factor receptor / Corticotropin-releasing factor family / 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 / 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 Corticoliberin / Corticotropin-releasing factor receptor 1 / 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 : 2.91 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, 5件 詳細 詳細を隠すOrganization Grant number 国 National Health and Medical Research Council (Australia) 1120919 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 Science and Technology 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8月21日 - マップ公開 2020年2月5日 - 更新 2025年6月4日 - 現状 2025年6月4日 処理サイト : RCSB / 状態 : 公開
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