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 / positive regulation of inositol trisphosphate biosynthetic process / Hormone ligand-binding receptors / ovulation cycle process / cellular response to gonadotropin stimulus ...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 / positive regulation of inositol trisphosphate biosynthetic process / Hormone ligand-binding receptors / ovulation cycle process / cellular response to gonadotropin stimulus / positive regulation of hormone biosynthetic process / cellular response to luteinizing hormone stimulus / male genitalia development / protein targeting to lysosome / G protein-coupled peptide receptor activity / arachidonic acid secretion / positive regulation of calcium ion transport into cytosol / seminiferous tubule development / uterus development / peptide hormone binding / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / centriolar satellite / positive regulation of calcium-mediated signaling / ovarian follicle development / activation of adenylate cyclase activity / hormone-mediated signaling pathway / positive regulation of release of sequestered calcium ion into cytosol / adenylate cyclase-activating G protein-coupled receptor signaling pathway / cognition / male gonad development / phospholipase C-activating G protein-coupled receptor signaling pathway / ATPase binding / G alpha (s) signalling events / spermatogenesis / receptor complex / endosome / response to xenobiotic stimulus / G protein-coupled receptor signaling pathway / extracellular space / identical protein binding / plasma membrane 類似検索 - 分子機能
Lutropin-choriogonadotropic hormone receptor / Glycoprotein hormone receptor family / BspA type Leucine rich repeat region / BspA type Leucine rich repeat region (6 copies) / Leucine-rich repeat domain superfamily / 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) 類似検索 - ドメイン・相同性
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.