登録情報 データベース : EMDB / ID : EMD-31457 構造の表示 ダウンロードとリンクタイトル Cryo-EM structure of afamelanotide-MC4R-Gs_Nb35 complex マップデータ 詳細 試料複合体 : Complex of afamelanotide bound MC4R-Gs protein複合体 : Dominant Negative Guanine nucleotide-binding protein G(s) subunit alpha isoformsタンパク質・ペプチド : Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short複合体 : 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(T) subunit beta-1複合体 : Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2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 : Nanobody35複合体 : melanocrotin-4 receptorタンパク質・ペプチド : Melanocortin receptor 4複合体 : afamelanotideタンパク質・ペプチド : afamelanotide 残り2件を表示 表示を減らすリガンド : CALCIUM IONリガンド : water 詳細 キーワード single particle / membrane protein / Class A G-protein-coupled receptors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 eating behavior / response to bisphenol A / response to melanocyte-stimulating hormone / melanocyte-stimulating hormone receptor activity / melanocortin receptor activity / regulation of grooming behavior / energy reserve metabolic process / neuropeptide binding / feeding behavior / insulin secretion ... regulation of eating behavior / response to bisphenol A / response to melanocyte-stimulating hormone / melanocyte-stimulating hormone receptor activity / melanocortin receptor activity / regulation of grooming behavior / energy reserve metabolic process / neuropeptide binding / feeding behavior / insulin secretion / regulation of metabolic process / response to food / negative regulation of feeding behavior / diet induced thermogenesis / peptide hormone binding / positive regulation of bone resorption / Transcriptional and post-translational regulation of MITF-M expression and activity / Peptide ligand-binding receptors / response to insulin / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / 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 / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / adenylate cyclase-activating dopamine receptor signaling pathway / GPER1 signaling / Inactivation, recovery and regulation of the phototransduction cascade / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / sensory perception of taste / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / Ca2+ pathway / retina development in camera-type eye / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / fibroblast proliferation / G alpha (i) signalling events / 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 (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell population proliferation / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / ubiquitin protein ligase binding / protein-containing complex binding / signal transduction / extracellular exosome / membrane / plasma membrane / cytosol / cytoplasm 類似検索 - 分子機能 Melanocortin 4 receptor / Melanocortin receptor 3-5 / Melanocortin/ACTH receptor / Serpentine type 7TM GPCR chemoreceptor Srsx / 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 ... Melanocortin 4 receptor / Melanocortin receptor 3-5 / Melanocortin/ACTH receptor / Serpentine type 7TM GPCR chemoreceptor Srsx / 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 / 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. / WD domain, G-beta repeat / 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 類似検索 - ドメイン・相同性 Melanocortin receptor 4 / 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 / Isoform Gnas-2 of 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) / 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Zhang H / Chen L 引用ジャーナル : Cell Res / 年 : 2021タイトル : Structural insights into ligand recognition and activation of the melanocortin-4 receptor.著者: Huibing Zhang / Li-Nan Chen / Dehua Yang / Chunyou Mao / Qingya Shen / Wenbo Feng / Dan-Dan Shen / Antao Dai / Shanshan Xie / Yan Zhou / Jiao Qin / Jin-Peng Sun / Daniel H Scharf / Tingjun ... 著者 : Huibing Zhang / Li-Nan Chen / Dehua Yang / Chunyou Mao / Qingya Shen / Wenbo Feng / Dan-Dan Shen / Antao Dai / Shanshan Xie / Yan Zhou / Jiao Qin / Jin-Peng Sun / Daniel H Scharf / Tingjun Hou / Tianhua Zhou / Ming-Wei Wang / Yan Zhang / 要旨 : Melanocortin-4 receptor (MC4R) plays a central role in the regulation of energy homeostasis. Its high sequence similarity to other MC receptor family members, low agonist selectivity and the lack of ... Melanocortin-4 receptor (MC4R) plays a central role in the regulation of energy homeostasis. Its high sequence similarity to other MC receptor family members, low agonist selectivity and the lack of structural information concerning MC4R-specific activation have hampered the development of MC4R-seletive therapeutics to treat obesity. Here, we report four high-resolution structures of full-length MC4R in complex with the heterotrimeric G protein stimulated by the endogenous peptide ligand α-MSH, FDA-approved drugs afamelanotide (Scenesse™) and bremelanotide (Vyleesi™), and a selective small-molecule ligand THIQ, respectively. Together with pharmacological studies, our results reveal the conserved binding mode of peptidic agonists, the distinctive molecular details of small-molecule agonist recognition underlying receptor subtype selectivity, and a distinct activation mechanism for MC4R, thereby offering new insights into G protein coupling. Our work may facilitate the discovery of selective therapeutic agents targeting MC4R. 履歴 登録 2021年6月21日 - ヘッダ(付随情報) 公開 2021年11月3日 - マップ公開 2021年11月3日 - 更新 2024年10月16日 - 現状 2024年10月16日 処理サイト : PDBj / 状態 : 公開
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