登録情報 データベース : EMDB / ID : EMD-35135 ダウンロードとリンクタイトル FSHR-Follicle stimulating hormone-compound 716340-Gs complex マップデータDeepEMhancer sharpen 詳細 試料複合体 : FSHR-Follicle stimulating hormone-compound 716340-Gs complexリガンド : x 5種 詳細 キーワード Follicle stimulating hormone / FSH / GPCR / Gs-protein / HORMONE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
follicle-stimulating hormone receptor activity / regulation of platelet-derived growth factor receptor signaling pathway / regulation of acetylcholine metabolic process / progesterone biosynthetic process / regulation of protein kinase A signaling / regulation of hormone metabolic process / positive regulation of steroid biosynthetic process / follicle-stimulating hormone activity / follicle-stimulating hormone complex / pituitary gonadotropin complex ... follicle-stimulating hormone receptor activity / regulation of platelet-derived growth factor receptor signaling pathway / regulation of acetylcholine metabolic process / progesterone biosynthetic process / regulation of protein kinase A signaling / regulation of hormone metabolic process / positive regulation of steroid biosynthetic process / follicle-stimulating hormone activity / follicle-stimulating hormone complex / pituitary gonadotropin complex / luteinizing hormone secretion / follicle-stimulating hormone secretion / Thyroxine biosynthesis / Mineralocorticoid biosynthesis / adenylate cyclase-activating serotonin receptor signaling pathway / primary ovarian follicle growth / Glycoprotein hormones / Reactions specific to the complex N-glycan synthesis pathway / Hormone ligand-binding receptors / Androgen biosynthesis / follicle-stimulating hormone signaling pathway / female gamete generation / Sertoli cell proliferation / gonad development / intracellular water homeostasis / sperm DNA condensation / negative regulation of organ growth / Sertoli cell development / sensory perception of chemical stimulus / basement membrane organization / regulation of osteoclast differentiation / transcytosis / cellular response to follicle-stimulating hormone stimulus / regulation of systemic arterial blood pressure / female gonad development / regulation of signaling receptor activity / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / thyroid hormone generation / positive regulation of bone resorption / G protein-coupled peptide receptor activity / beta-2 adrenergic receptor binding / negative regulation of bone resorption / organ growth / positive regulation of intracellular estrogen receptor signaling pathway / regulation of chromosome organization / uterus development / peptide hormone binding / thyroid gland development / PKA activation in glucagon signalling / developmental growth / D1 dopamine receptor binding / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway / response to prostaglandin E / hormone-mediated signaling pathway / adenylate cyclase regulator activity / insulin-like growth factor receptor binding / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / ionotropic glutamate receptor binding / transforming growth factor beta receptor signaling pathway / adenylate cyclase activator activity / locomotory behavior / female pregnancy / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / hormone activity / bone development / platelet aggregation / Golgi lumen / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / male gonad development / 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 / neuron projection development / 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 / 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 類似検索 - 分子機能 Follicle stimulating hormone receptor / Gonadotropin hormone receptor, transmembrane domain / Gonadotropin hormone receptor transmembrane region / 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. ... Follicle stimulating hormone receptor / Gonadotropin hormone receptor, transmembrane domain / Gonadotropin hormone receptor transmembrane region / 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 / BspA type Leucine rich repeat region (6 copies) / Glycoprotein hormone receptor family / Leucine rich repeat N-terminal domain / Leucine-rich repeat N-terminal domain / Leucine rich repeat N-terminal domain / 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 / 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 / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性 Glycoprotein hormones alpha chain / Follitropin subunit beta / Follicle-stimulating hormone 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 XLas / Guanine nucleotide-binding protein G(s) subunit alpha 類似検索 - 構成要素生物種 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 : 2.8 Å 詳細 データ登録者Duan J / Xu P / Yang J / Ji Y / Zhang H / Mao C / Luan X / Jiang Y / Zhang Y / Zhang S / 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 : Nat Commun / 年 : 2023タイトル : Mechanism of hormone and allosteric agonist mediated activation of follicle stimulating hormone receptor.著者 : Jia Duan / Peiyu Xu / Huibing Zhang / Xiaodong Luan / Jiaqi Yang / Xinheng He / Chunyou Mao / Dan-Dan Shen / Yujie Ji / Xi Cheng / Hualiang Jiang / Yi Jiang / Shuyang Zhang / Yan Zhang / H Eric Xu / 要旨 : Follicle stimulating hormone (FSH) is an essential glycoprotein hormone for human reproduction, which functions are mediated by a G protein-coupled receptor, FSHR. Aberrant FSH-FSHR signaling causes ... Follicle stimulating hormone (FSH) is an essential glycoprotein hormone for human reproduction, which functions are mediated by a G protein-coupled receptor, FSHR. Aberrant FSH-FSHR signaling causes infertility and ovarian hyperstimulation syndrome. Here we report cryo-EM structures of FSHR in both inactive and active states, with the active structure bound to FSH and an allosteric agonist compound 21 f. The structures of FSHR are similar to other glycoprotein hormone receptors, highlighting a conserved activation mechanism of hormone-induced receptor activation. Compound 21 f formed extensive interactions with the TMD to directly activate FSHR. Importantly, the unique residue H615 in FSHR plays an essential role in determining FSHR selectivity for various allosteric agonists. Together, our structures provide a molecular basis of FSH and small allosteric agonist-mediated FSHR activation, which could inspire the design of FSHR-targeted drugs for the treatment of infertility and controlled ovarian stimulation for in vitro fertilization. 履歴 登録 2023年1月14日 - ヘッダ(付随情報) 公開 2023年3月29日 - マップ公開 2023年3月29日 - 更新 2024年11月20日 - 現状 2024年11月20日 処理サイト : PDBj / 状態 : 公開
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