登録情報 データベース : EMDB / ID : EMD-20284 構造の表示 ダウンロードとリンクタイトル Cryo-EM structure of Urocortin 1-bound Corticotropin-releasing factor 1 receptor in complex with Gs protein and Nb35 マップデータ 詳細 試料複合体 : Urocortin1-bound CRF1R in complex Gs and Nb35タンパク質・ペプチド : Corticotropin-releasing factor receptor 1タンパク質・ペプチド : Urocortinタンパク質・ペプチド : Guanine nucleotide-binding protein G(s) subunit alpha isoforms short,Guanine nucleotide-binding protein G(i) subunit alpha-1,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 : Nanobody 35 残り2件を表示 表示を減らすリガンド : CHOLESTEROLリガンド : PALMITIC ACID 詳細機能・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
regulation of adenylate cyclase activity involved in G protein-coupled receptor signaling pathway / corticotropin-releasing hormone binding / histone deacetylase inhibitor activity / regulation of corticosterone secretion / corticotrophin-releasing factor receptor activity / corticotropin-releasing hormone receptor activity / corticotropin-releasing hormone receptor 2 binding / corticotropin secretion / positive regulation of corticotropin secretion / general adaptation syndrome, behavioral process ... regulation of adenylate cyclase activity involved in G protein-coupled receptor signaling pathway / corticotropin-releasing hormone binding / histone deacetylase inhibitor activity / regulation of corticosterone secretion / corticotrophin-releasing factor receptor activity / corticotropin-releasing hormone receptor activity / corticotropin-releasing hormone receptor 2 binding / corticotropin secretion / positive regulation of corticotropin secretion / general adaptation syndrome, behavioral process / positive regulation of behavioral fear response / parturition / negative regulation of hormone secretion / cellular response to corticotropin-releasing hormone stimulus / negative regulation of voltage-gated calcium channel activity / varicosity / behavioral response to ethanol / response to auditory stimulus / drinking behavior / positive regulation of cAMP-mediated signaling / negative regulation of appetite / positive regulation of vascular permeability / fear response / neuropeptide hormone activity / negative regulation of cell size / G protein-coupled peptide receptor activity / Class B/2 (Secretin family receptors) / exploration behavior / adrenal gland development / response to pain / negative regulation of feeding behavior / positive regulation of calcium ion import / startle response / associative learning / PKA activation in glucagon signalling / social behavior / hair follicle placode formation / mu-type opioid receptor binding / developmental growth / corticotropin-releasing hormone receptor 1 binding / positive regulation of collagen biosynthetic process / intracellular transport / D1 dopamine receptor binding / Synthesis, secretion, and deacylation of Ghrelin / Adenylate cyclase inhibitory pathway / neuropeptide signaling pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / Hedgehog 'off' state / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / beta-2 adrenergic receptor binding / axon terminus / adenylate cyclase-activating adrenergic receptor signaling pathway / response to glucocorticoid / regulation of mitotic spindle organization / cellular response to forskolin / regulation of synaptic transmission, glutamatergic / positive regulation of cardiac muscle contraction / activation of adenylate cyclase activity / adenylate cyclase activator activity / negative regulation of blood pressure / aerobic respiration / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / trans-Golgi network membrane / positive regulation of DNA replication / Regulation of insulin secretion / positive regulation of translation / G protein-coupled receptor binding / female pregnancy / sensory perception of sound / 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 / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / 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 activation / G protein-coupled acetylcholine receptor signaling pathway / 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 / response to peptide hormone / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / platelet aggregation / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins 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. / Hormone receptor domain ... 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. / Hormone receptor domain / GPCR, family 2, extracellular hormone receptor domain / G-protein coupled receptors family 2 profile 1. / Domain present in hormone receptors / 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, group I / G-alpha domain profile. / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G protein alpha subunit / G-protein, gamma subunit / G-protein gamma subunit domain profile. / GGL domain / G-protein gamma-like domain superfamily / G-protein gamma-like domain / GGL domain / G protein gamma subunit-like motifs / 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. / WD domain, G-beta repeat / 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 Corticotropin-releasing factor receptor 1 / Urocortin / 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 / Guanine nucleotide-binding protein G(i) subunit alpha-1 類似検索 - 構成要素生物種 Homo sapiens (ヒト) / synthetic construct (人工物) 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Ma S / Shen Q / Zhao L-H / Mao C / Zhou XE / Shen D-D / de Waal PW / Bi P / Li C / Jiang Y ...Ma S / Shen Q / Zhao L-H / Mao C / Zhou XE / Shen D-D / de Waal PW / Bi P / Li C / Jiang Y / Wang M-W / Sexton PM / Wootten D / Melcher K / Zhang Y / Xu HE 資金援助 米国, 中国, 2件 詳細 詳細を隠すOrganization Grant number 国 National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) GM127710 米国 National Natural Science Foundation of China (NSFC) 31770796 中国
引用ジャーナル : Mol Cell / 年 : 2020タイトル : Molecular Basis for Hormone Recognition and Activation of Corticotropin-Releasing Factor Receptors.著者: Shanshan Ma / Qingya Shen / Li-Hua Zhao / Chunyou Mao / X Edward Zhou / Dan-Dan Shen / Parker W de Waal / Peng Bi / Chuntao Li / Yi Jiang / Ming-Wei Wang / Patrick M Sexton / Denise Wootten / ... 著者 : Shanshan Ma / Qingya Shen / Li-Hua Zhao / Chunyou Mao / X Edward Zhou / Dan-Dan Shen / Parker W de Waal / Peng Bi / Chuntao Li / Yi Jiang / Ming-Wei Wang / Patrick M Sexton / Denise Wootten / Karsten Melcher / Yan Zhang / H Eric Xu / 要旨 : Corticotropin-releasing factor (CRF) and the three related peptides urocortins 1-3 (UCN1-UCN3) are endocrine hormones that control the stress responses by activating CRF1R and CRF2R, two members of ... Corticotropin-releasing factor (CRF) and the three related peptides urocortins 1-3 (UCN1-UCN3) are endocrine hormones that control the stress responses by activating CRF1R and CRF2R, two members of class B G-protein-coupled receptors (GPCRs). Here, we present two cryoelectron microscopy (cryo-EM) structures of UCN1-bound CRF1R and CRF2R with the stimulatory G protein. In both structures, UCN1 adopts a single straight helix with its N terminus dipped into the receptor transmembrane bundle. Although the peptide-binding residues in CRF1R and CRF2R are different from other members of class B GPCRs, the residues involved in receptor activation and G protein coupling are conserved. In addition, both structures reveal bound cholesterol molecules to the receptor transmembrane helices. Our structures define the basis of ligand-binding specificity in the CRF receptor-hormone system, establish a common mechanism of class B GPCR activation and G protein coupling, and provide a paradigm for studying membrane protein-lipid interactions for class B GPCRs. 履歴 登録 2019年6月12日 - ヘッダ(付随情報) 公開 2020年1月29日 - マップ公開 2020年2月12日 - 更新 2020年2月19日 - 現状 2020年2月19日 処理サイト : RCSB / 状態 : 公開
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