登録情報 データベース : EMDB / ID : EMD-31598 構造の表示 ダウンロードとリンクタイトル luteinizing hormone/choriogonadotropin receptor-chorionic gonadotropin-Gs complex マップデータ 詳細 試料複合体 : luteinizing hormone/choriogonadotropin receptor-chorionic gonadotropin-Gs complex複合体 : Glycoprotein hormones alpha chainタンパク質・ペプチド : Glycoprotein hormones alpha chain複合体 : Lutropin-choriogonadotropic hormone receptorタンパク質・ペプチド : Lutropin-choriogonadotropic hormone receptor複合体 : Choriogonadotropin subunit beta 3タンパク質・ペプチド : Choriogonadotropin subunit beta 3複合体 : Gs proteinsタンパク質・ペプチド : Engineered Guanine nucleotide-binding protein G(s) subunit alphaタンパク質・ペプチド : 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(O) subunit gamma-2 詳細機能・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
luteinizing hormone receptor activity / choriogonadotropin hormone receptor activity / choriogonadotropin hormone binding / regulation of steroid hormone biosynthetic process / development of secondary male sexual characteristics / luteinizing hormone signaling pathway / follicle-stimulating hormone activity / follicle-stimulating hormone complex / pituitary gonadotropin complex / luteinizing hormone secretion ... luteinizing hormone receptor activity / choriogonadotropin hormone receptor activity / choriogonadotropin hormone binding / regulation of steroid hormone biosynthetic process / development of secondary male sexual characteristics / luteinizing hormone signaling pathway / follicle-stimulating hormone activity / follicle-stimulating hormone complex / pituitary gonadotropin complex / luteinizing hormone secretion / follicle-stimulating hormone secretion / positive regulation of steroid biosynthetic process / ovulation / Thyroxine biosynthesis / Mineralocorticoid biosynthesis / positive regulation of inositol trisphosphate biosynthetic process / Hormone ligand-binding receptors / Glycoprotein hormones / Reactions specific to the complex N-glycan synthesis pathway / Androgen biosynthesis / follicle-stimulating hormone signaling pathway / ovulation cycle process / female gamete generation / cellular response to gonadotropin stimulus / positive regulation of hormone biosynthetic process / negative regulation of organ growth / cellular response to luteinizing hormone stimulus / male genitalia development / protein targeting to lysosome / thyroid hormone generation / G-protein activation / Activation of the phototransduction cascade / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Ca2+ pathway / G alpha (z) signalling events / G protein-coupled peptide receptor activity / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Adrenaline,noradrenaline inhibits insulin secretion / regulation of signaling receptor activity / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / G alpha (i) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / alkylglycerophosphoethanolamine phosphodiesterase activity / ADP signalling through P2Y purinoceptor 12 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / G alpha (q) signalling events / photoreceptor outer segment membrane / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / arachidonic acid secretion / organ growth / positive regulation of calcium ion transport into cytosol / spectrin binding / Vasopressin regulates renal water homeostasis via Aquaporins / seminiferous tubule development / uterus development / peptide hormone binding / thyroid gland development / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / centriolar satellite / photoreceptor outer segment / positive regulation of calcium-mediated signaling / ovarian follicle development / cardiac muscle cell apoptotic process / activation of adenylate cyclase activity / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / hormone-mediated signaling pathway / photoreceptor inner segment / positive regulation of release of sequestered calcium ion into cytosol / adenylate cyclase-activating G protein-coupled receptor signaling pathway / hormone activity / cognition 類似検索 - 分子機能 Lutropin-choriogonadotropic hormone 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. ... Lutropin-choriogonadotropic hormone 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 / Glycoprotein hormone receptor family / BspA type Leucine rich repeat region / BspA type Leucine rich repeat region (6 copies) / Cystine-knot cytokine / Leucine-rich repeat domain superfamily / G-protein, gamma subunit / G-protein gamma subunit domain profile. / GGL domain / G-protein gamma-like domain superfamily / G-protein gamma-like domain / GGL domain / G protein gamma subunit-like motifs / 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. / WD domain, G-beta repeat / 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 Glycoprotein hormones alpha chain / Choriogonadotropin subunit beta 3 / Lutropin-choriogonadotropic hormone receptor / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 類似検索 - 構成要素生物種 Homo sapiens (ヒト) / Bos taurus (ウシ) / Rattus norvegicus (ドブネズミ)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 4.3 Å 詳細 データ登録者Duan J / Xu P / Cheng X / Mao C / Croll T / He X / Shi J / Luan X / Yin W / You E ...Duan J / Xu P / Cheng X / Mao C / Croll T / He X / Shi J / Luan X / Yin W / You E / Liu Q / Zhang S / Jiang H / Zhang Y / Jiang Y / Xu HE 資金援助 中国, 1件 詳細 詳細を隠すOrganization Grant number 国 Ministry of Science and Technology (MoST, China) 2018YFA0507002 中国
引用ジャーナル : Nature / 年 : 2021タイトル : Structures of full-length glycoprotein hormone receptor signalling complexes.著者: Jia Duan / Peiyu Xu / Xi Cheng / Chunyou Mao / Tristan Croll / Xinheng He / Jingjing Shi / Xiaodong Luan / Wanchao Yin / Erli You / Qiufeng Liu / Shuyang Zhang / Hualiang Jiang / Yan Zhang / ... 著者 : Jia Duan / Peiyu Xu / Xi Cheng / Chunyou Mao / Tristan Croll / Xinheng He / Jingjing Shi / Xiaodong Luan / Wanchao Yin / Erli You / Qiufeng Liu / Shuyang Zhang / Hualiang Jiang / Yan Zhang / Yi Jiang / H Eric Xu / 要旨 : Luteinizing hormone and chorionic gonadotropin are glycoprotein hormones that are related to follicle-stimulating hormone and thyroid-stimulating hormone. Luteinizing hormone and chorionic ... Luteinizing hormone and chorionic gonadotropin are glycoprotein hormones that are related to follicle-stimulating hormone and thyroid-stimulating hormone. Luteinizing hormone and chorionic gonadotropin are essential to human reproduction and are important therapeutic drugs. They activate the same G-protein-coupled receptor, luteinizing hormone-choriogonadotropin receptor (LHCGR), by binding to the large extracellular domain. Here we report four cryo-electron microscopy structures of LHCGR: two structures of the wild-type receptor in the inactive and active states; and two structures of the constitutively active mutated receptor. The active structures are bound to chorionic gonadotropin and the stimulatory G protein (G), and one of the structures also contains Org43553, an allosteric agonist. The structures reveal a distinct 'push-and-pull' mechanism of receptor activation, in which the extracellular domain is pushed by the bound hormone and pulled by the extended hinge loop next to the transmembrane domain. A highly conserved 10-residue fragment (P10) from the hinge C-terminal loop at the interface between the extracellular domain and the transmembrane domain functions as a tethered agonist to induce conformational changes in the transmembrane domain and G-protein coupling. Org43553 binds to a pocket of the transmembrane domain and interacts directly with P10, which further stabilizes the active conformation. Together, these structures provide a common model for understanding the signalling of glycoprotein hormone receptors and a basis for drug discovery for endocrine diseases. 履歴 登録 2021年7月31日 - ヘッダ(付随情報) 公開 2021年9月29日 - マップ公開 2021年9月29日 - 更新 2022年2月16日 - 現状 2022年2月16日 処理サイト : PDBj / 状態 : 公開
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