登録情報 データベース : PDB / ID : 8gy7 構造の表示 ダウンロードとリンクタイトル Cryo-EM structure of ACTH-bound melanocortin-2 receptor in complex with MRAP1 and Gs protein 要素(Guanine nucleotide-binding protein ...) x 3 Corticotropin Melanocortin-2 receptor accessory protein Soluble cytochrome b562,Adrenocorticotropic hormone receptor,melanocortin-2 receptor,Adrenocorticotropic hormone receptor,Adrenocorticotropic hormone receptor 詳細キーワード MEMBRANE PROTEIN / melanocortin-2 receptor / MRAP1 / GPCR / ACTH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 receptor activity / corticotropin hormone receptor binding / type 5 melanocortin receptor binding / Defective ACTH causes obesity and POMCD / type 1 melanocortin receptor binding / type 3 melanocortin receptor binding / type 4 melanocortin receptor binding / melanocortin receptor activity / signaling receptor regulator activity / sensory perception of chemical stimulus ... corticotropin receptor activity / corticotropin hormone receptor binding / type 5 melanocortin receptor binding / Defective ACTH causes obesity and POMCD / type 1 melanocortin receptor binding / type 3 melanocortin receptor binding / type 4 melanocortin receptor binding / melanocortin receptor activity / signaling receptor regulator activity / sensory perception of chemical stimulus / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / negative regulation of adenylate cyclase activity / negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / regulation of metabolic process / GTP metabolic process / negative regulation of protein localization to plasma membrane / beta-2 adrenergic receptor binding / G protein-coupled dopamine receptor signaling pathway / positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / PKA activation in glucagon signalling / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / positive regulation of macroautophagy / developmental growth / D1 dopamine receptor binding / Adenylate cyclase inhibitory pathway / Hedgehog 'off' state / insulin-like growth factor receptor binding / adenylate cyclase activator activity / ionotropic glutamate receptor binding / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Peptide ligand-binding receptors / protein localization to plasma membrane / G protein-coupled receptor binding / G protein-coupled receptor activity / electron transport chain / 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-coupled acetylcholine receptor signaling pathway / G-protein activation / hormone activity / 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 / platelet aggregation / 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 / 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 / GPER1 signaling / GDP binding / 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 / 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 / midbody / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell population proliferation / periplasmic space / electron transfer activity / apical plasma membrane / iron ion binding / G protein-coupled receptor signaling pathway 類似検索 - 分子機能 Adrenocorticotrophin (ACTH) receptor / Melanocortin-2 receptor accessory protein family / Melanocortin-2 receptor accessory protein family / Pro-opiomelanocortin / Pro-opiomelanocortin/corticotropin, ACTH, central region / Corticotropin ACTH domain / Corticotropin ACTH domain / Melanocortin/ACTH receptor / Cytochrome b562 / Cytochrome b562 ... Adrenocorticotrophin (ACTH) receptor / Melanocortin-2 receptor accessory protein family / Melanocortin-2 receptor accessory protein family / Pro-opiomelanocortin / Pro-opiomelanocortin/corticotropin, ACTH, central region / Corticotropin ACTH domain / Corticotropin ACTH domain / Melanocortin/ACTH receptor / Cytochrome b562 / Cytochrome b562 / G-protein alpha subunit, group S / Cytochrome c/b562 / G-protein alpha subunit, group I / Serpentine type 7TM GPCR chemoreceptor Srsx / 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 coupled receptors family 1 signature. / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / 7 transmembrane receptor (rhodopsin family) / 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 Guanine nucleotide-binding protein G(i) subunit alpha-3 / Soluble cytochrome b562 / 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 / Pro-opiomelanocortin / Adrenocorticotropic hormone receptor / Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas / Melanocortin-2 receptor accessory protein 類似検索 - 構成要素生物種 Homo sapiens (ヒト)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 : 3.3 Å 詳細データ登録者 Luo, P. / Feng, W.B. / Ma, S.S. / Dai, A.T. / Yuan, Q.N. / Wu, K. / Yang, D.H. / Wang, M.W. / Xu, H.E. / Jiang, Y. 資金援助 中国, 1件 詳細 詳細を隠す組織 認可番号 国 National Natural Science Foundation of China (NSFC) 32171187 中国
引用ジャーナル : Cell Res / 年 : 2023タイトル : Structural basis of signaling regulation of the human melanocortin-2 receptor by MRAP1.著者 : Ping Luo / Wenbo Feng / Shanshan Ma / Antao Dai / Kai Wu / Xianyue Chen / Qingning Yuan / Xiaoqing Cai / Dehua Yang / Ming-Wei Wang / H Eric Xu / Yi Jiang / 要旨 : G protein-coupled receptors (GPCRs) are regulated by various downstream proteins, of which the melanocortin receptor accessory protein 1 (MRAP1) is closely involved in the regulation of melanocortin ... G protein-coupled receptors (GPCRs) are regulated by various downstream proteins, of which the melanocortin receptor accessory protein 1 (MRAP1) is closely involved in the regulation of melanocortin receptor 2 (MC2R). Assisted by MRAP1, MC2R responds to adrenocorticotropic hormone (ACTH) and stimulates glucocorticoid biogenesis and cortisol secretion. MC2R activation plays an essential role in the hypothalamic-pituitary-adrenal (HPA) axis that regulates stress response, while its dysfunction causes glucocorticoid insufficiency- or cortisol excess-associated disorders. Here, we present a cryo-electron microscopy (cryo-EM) structure of the ACTH-bound MC2R-G-MRAP1 complex. Our structure, together with mutagenesis analysis, reveals a unique sharp kink at the extracellular region of MRAP1 and the 'seat-belt' effect of MRAP1 on stabilizing ACTH binding and MC2R activation. Mechanisms of ACTH recognition by MC2R and receptor activation are also demonstrated. These findings deepen our understanding of GPCR regulation by accessory proteins and provide valuable insights into the ab initio design of therapeutic agents targeting MC2R. 履歴 登録 2022年9月21日 登録サイト : PDBJ / 処理サイト : PDBE改定 1.0 2023年1月11日 Provider : repository / タイプ : Initial release