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 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 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 / regulation of signaling receptor activity / Thyroxine biosynthesis / Mineralocorticoid biosynthesis / Glycoprotein hormones / primary ovarian follicle growth / Hormone ligand-binding receptors / Reactions specific to the complex N-glycan synthesis pathway / Androgen biosynthesis / follicle-stimulating hormone signaling pathway / female gamete generation / Sertoli cell proliferation / gonad development / intracellular water homeostasis / sperm DNA condensation / Sertoli cell development / negative regulation of organ growth / basement membrane organization / cellular response to follicle-stimulating hormone stimulus / transcytosis / regulation of systemic arterial blood pressure / regulation of osteoclast differentiation / sensory perception of chemical stimulus / mu-type opioid receptor binding / thyroid hormone generation / corticotropin-releasing hormone receptor 1 binding / positive regulation of bone resorption / G protein-coupled peptide receptor activity / negative regulation of bone resorption / organ growth / beta-2 adrenergic receptor binding / positive regulation of intracellular estrogen receptor signaling pathway / female gonad development / regulation of chromosome organization / uterus development / thyroid gland development / peptide hormone binding / PKA activation in glucagon signalling / developmental growth / D1 dopamine receptor binding / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway / insulin-like growth factor receptor binding / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / hormone-mediated signaling pathway / transforming growth factor beta receptor signaling pathway / ionotropic glutamate receptor binding / adenylate cyclase activator activity / locomotory behavior / female pregnancy / hormone activity / bone development / Golgi lumen / platelet aggregation / male gonad development / G-protein beta/gamma-subunit complex binding / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / neuron projection development / G protein-coupled acetylcholine receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / 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 / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / ADORA2B mediated anti-inflammatory cytokines production / G beta:gamma signalling through PI3Kgamma / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / cellular response to prostaglandin E stimulus / heterotrimeric G-protein complex 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 / BspA type Leucine rich repeat region / Cystine-knot domain / 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 / G protein alpha subunit, helical insertion / G protein alpha subunit / Guanine nucleotide binding protein (G-protein), alpha subunit / G-protein alpha subunit / G-alpha domain profile. / 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. / 7 transmembrane receptor (rhodopsin family) / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / 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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