登録情報 データベース : EMDB / ID : EMD-33492 ダウンロードとリンクタイトル TSHR-Gs-M22 antibody-ML109 complex マップデータ 詳細 試料複合体 : The complex was assembled by co-expression.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 / M22 / scFv / 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
thyroid-stimulating hormone signaling pathway / cellular response to thyrotropin-releasing hormone / thyroid-stimulating hormone receptor activity / cellular response to glycoprotein / Hormone ligand-binding receptors / G protein-coupled peptide receptor activity / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / hormone-mediated signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade ... thyroid-stimulating hormone signaling pathway / cellular response to thyrotropin-releasing hormone / thyroid-stimulating hormone receptor activity / cellular response to glycoprotein / Hormone ligand-binding receptors / G protein-coupled peptide receptor activity / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / hormone-mediated 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 / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / adenylate cyclase-activating G protein-coupled receptor signaling pathway / 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 / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / ADP signalling through P2Y purinoceptor 1 / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / 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 / cell-cell signaling / G alpha (12/13) signalling events / sensory perception of taste / extracellular vesicle / signaling receptor activity / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / positive regulation of cold-induced thermogenesis / retina development in camera-type eye / GTPase binding / Ca2+ pathway / fibroblast proliferation / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / basolateral plasma membrane / G alpha (q) signalling events / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell surface receptor signaling pathway / cell population proliferation / receptor complex / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / positive regulation of cell population proliferation / synapse / protein-containing complex binding / cell surface / signal transduction / extracellular exosome / membrane / plasma membrane / cytosol / cytoplasm 類似検索 - 分子機能 Thyrotropin receptor / BspA type Leucine rich repeat region / BspA type Leucine rich repeat region (6 copies) / Glycoprotein hormone receptor family / Leucine-rich repeat domain superfamily / G-protein, gamma subunit / G-protein gamma subunit domain profile. / G-protein gamma-like domain / G-protein gamma-like domain superfamily / GGL domain ... Thyrotropin receptor / BspA type Leucine rich repeat region / BspA type Leucine rich repeat region (6 copies) / Glycoprotein hormone receptor family / Leucine-rich repeat domain superfamily / 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 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. / 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 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 類似検索 - 構成要素生物種 Homo sapiens (ヒト) / Mus musculus (ハツカネズミ)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 2.78 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17日 - マップ公開 2022年8月17日 - 更新 2024年10月9日 - 現状 2024年10月9日 処理サイト : PDBj / 状態 : 公開
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