登録情報 データベース : EMDB / ID : EMD-33491 ダウンロードとリンクタイトル TSHR-thyroid stimulating hormone-Gs-ML109 complex マップデータA b-factor-sharpen map. 詳細 試料複合体 : TSHR-thyroid stimulating hormone-Gs-ML109 complexリガンド : x 4種 詳細 キーワード thyroid-stimulating hormone / thyroid-stimulating hormone receptor / THS / THSR / GPCR / Gs / ML-109 / 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
regulation of parathyroid hormone secretion / post-embryonic body morphogenesis / thyroid-stimulating hormone signaling pathway / cellular response to thyrotropin-releasing hormone / thyroid-stimulating hormone receptor activity / cellular response to glycoprotein / follicle-stimulating hormone activity / follicle-stimulating hormone complex / pituitary gonadotropin complex / luteinizing hormone secretion ... regulation of parathyroid hormone secretion / post-embryonic body morphogenesis / thyroid-stimulating hormone signaling pathway / cellular response to thyrotropin-releasing hormone / thyroid-stimulating hormone receptor activity / cellular response to glycoprotein / follicle-stimulating hormone activity / follicle-stimulating hormone complex / pituitary gonadotropin complex / luteinizing hormone secretion / follicle-stimulating hormone secretion / positive regulation of steroid biosynthetic process / Thyroxine biosynthesis / Mineralocorticoid biosynthesis / Glycoprotein hormones / Reactions specific to the complex N-glycan synthesis pathway / Hormone ligand-binding receptors / Androgen biosynthesis / follicle-stimulating hormone signaling pathway / genomic imprinting / negative regulation of organ growth / tissue homeostasis / endochondral ossification / energy reserve metabolic process / thyroid hormone generation / embryonic cranial skeleton morphogenesis / regulation of signaling receptor activity / positive regulation of osteoclast differentiation / G protein-coupled peptide receptor activity / response to vitamin A / embryonic hindlimb morphogenesis / cartilage development / organ growth / skin development / alkylglycerophosphoethanolamine phosphodiesterase activity / thyroid gland development / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / anatomical structure morphogenesis / positive regulation of osteoblast differentiation / adenylate cyclase-activating adrenergic receptor signaling pathway / adenylate cyclase regulator activity / hormone-mediated signaling pathway / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / cellular response to glucagon stimulus / adenylate cyclase activator activity / post-embryonic development / skeletal system development / positive regulation of insulin secretion / hormone activity / multicellular organism growth / G-protein beta/gamma-subunit complex binding / Golgi lumen / 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 / response to estrogen / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / response to calcium ion / 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 / cell-cell signaling / extracellular vesicle / signaling receptor complex adaptor activity / signaling receptor activity / Thrombin signalling through proteinase activated receptors (PARs) / positive regulation of cold-induced thermogenesis / G protein activity / GTPase binding / Ca2+ pathway / retina development in camera-type eye 類似検索 - 分子機能 Thyrotropin receptor / Gonadotropin, beta subunit, conserved site / Glycoprotein hormones beta chain signature 1. / Glycoprotein hormones beta chain signature 2. / Glycoprotein hormone beta chain homologues. / Glycoprotein hormone alpha chain / Glycoprotein hormone / Glycoprotein hormones alpha chain signature 1. / Glycoprotein hormones alpha chain signature 2. / Glycoprotein hormones alpha chain family profile. ... Thyrotropin receptor / Gonadotropin, beta subunit, conserved site / Glycoprotein hormones beta chain signature 1. / Glycoprotein hormones beta chain signature 2. / Glycoprotein hormone beta chain homologues. / Glycoprotein hormone alpha chain / Glycoprotein hormone / Glycoprotein hormones alpha chain signature 1. / Glycoprotein hormones alpha chain signature 2. / Glycoprotein hormones alpha chain family profile. / Glycoprotein hormone alpha chain homologues. / Gonadotropin, beta subunit / Glycoprotein hormone subunit beta / Cystine-knot domain / BspA type Leucine rich repeat region / Glycoprotein hormone receptor family / BspA type Leucine rich repeat region (6 copies) / Cystine-knot cytokine / G-protein alpha subunit, group S / Leucine-rich repeat domain superfamily / 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 / 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 / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性 Glycoprotein hormones alpha chain / Thyrotropin subunit beta / Thyrotropin 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 (哺乳類) / 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 : 2.96 Å 詳細 データ登録者Duan J / Xu P / Luan X / Ji Y / Yuan Q / He X / Ye J / Cheng X / Jiang H / Zhang S ...Duan J / Xu P / Luan X / Ji Y / Yuan Q / He X / Ye J / Cheng X / Jiang H / Zhang S / Jiang Y / Xu HE 資金援助 中国, 1件 詳細 詳細を隠すOrganization Grant number 国 National Natural Science Foundation of China (NSFC) 32130022 中国
引用ジャーナル : Nature / 年 : 2022タイトル : Hormone- and antibody-mediated activation of the thyrotropin receptor.著者 : Jia Duan / Peiyu Xu / Xiaodong Luan / Yujie Ji / Xinheng He / Ning Song / Qingning Yuan / Ye Jin / Xi Cheng / Hualiang Jiang / Jie Zheng / Shuyang Zhang / Yi Jiang / H Eric Xu / 要旨 : Thyroid-stimulating hormone (TSH), through activation of its G-protein-coupled thyrotropin receptor (TSHR), controls the synthesis of thyroid hormone-an essential metabolic hormone. Aberrant ... Thyroid-stimulating hormone (TSH), through activation of its G-protein-coupled thyrotropin receptor (TSHR), controls the synthesis of thyroid hormone-an essential metabolic hormone. Aberrant signalling of TSHR by autoantibodies causes Graves' disease (hyperthyroidism) and hypothyroidism, both of which affect millions of patients worldwide. Here we report the active structures of TSHR with TSH and the activating autoantibody M22, both bound to the allosteric agonist ML-109, as well as an inactivated TSHR structure with the inhibitory antibody K1-70. Both TSH and M22 push the extracellular domain (ECD) of TSHR into an upright active conformation. By contrast, K1-70 blocks TSH binding and cannot push the ECD into the upright conformation. Comparisons of the active and inactivated structures of TSHR with those of the luteinizing hormone/choriogonadotropin receptor (LHCGR) reveal a universal activation mechanism of glycoprotein hormone receptors, in which a conserved ten-residue fragment (P10) from the hinge C-terminal loop mediates ECD interactions with the TSHR transmembrane domain. One notable feature is that there are more than 15 cholesterols surrounding TSHR, supporting its preferential location in lipid rafts. These structures also highlight a similar ECD-push mechanism for TSH and autoantibody M22 to activate TSHR, therefore providing the molecular basis for Graves' disease. 履歴 登録 2022年5月26日 - ヘッダ(付随情報) 公開 2022年8月24日 - マップ公開 2022年8月24日 - 更新 2024年11月13日 - 現状 2024年11月13日 処理サイト : PDBj / 状態 : 公開
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