+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-31599 | |||||||||
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タイトル | luteinizing hormone/choriogonadotropin receptor | |||||||||
マップデータ | ||||||||||
試料 |
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機能・相同性 | 機能・相同性情報 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 / peptide hormone binding / uterus development / 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 | |||||||||
生物種 | Homo sapiens (ヒト) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.8 Å | |||||||||
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
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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 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_31599.map.gz | 22.9 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-31599-v30.xml emd-31599.xml | 10.6 KB 10.6 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_31599.png | 45 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-31599 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-31599 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_31599_validation.pdf.gz | 309.7 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_31599_full_validation.pdf.gz | 309.2 KB | 表示 | |
XML形式データ | emd_31599_validation.xml.gz | 5.2 KB | 表示 | |
CIF形式データ | emd_31599_validation.cif.gz | 5.9 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31599 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31599 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_31599.map.gz / 形式: CCP4 / 大きさ: 27 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 1.045 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-試料の構成要素
-全体 : luteinizing hormone/choriogonadotropin receptor
全体 | 名称: luteinizing hormone/choriogonadotropin receptor |
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要素 |
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-超分子 #1: luteinizing hormone/choriogonadotropin receptor
超分子 | 名称: luteinizing hormone/choriogonadotropin receptor / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
-分子 #1: Lutropin-choriogonadotropic hormone receptor
分子 | 名称: Lutropin-choriogonadotropic hormone receptor / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 78.629797 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: DYKDDDDVEN LYFQGASALC PEPCNCVPDG ALRCPGPTAG LTRLSLAYLP VKVIPSQAFR GLNEVIKIEI SQIDSLERIE ANAFDNLLN LSEILIQNTK NLRYIEPGAF INLPRLKYLS ICNTGIRKFP DVTKVFSSES NFILEICDNL HITTIPGNAF Q GMNNESVT ...文字列: DYKDDDDVEN LYFQGASALC PEPCNCVPDG ALRCPGPTAG LTRLSLAYLP VKVIPSQAFR GLNEVIKIEI SQIDSLERIE ANAFDNLLN LSEILIQNTK NLRYIEPGAF INLPRLKYLS ICNTGIRKFP DVTKVFSSES NFILEICDNL HITTIPGNAF Q GMNNESVT LKLYGNGFEE VQSHAFNGTT LTSLELKENV HLEKMHNGAF RGATGPKTLD ISSTKLQALP SYGLESIQRL IA TSSYSLK KLPSRETFVN LLEATLTYPS HCCAFRNLPT KEQNFSHSIS ENFSKQCEST VRKVNNKTLY SSMLAESELS GWD YEYGFC LPKTPRCAPE PDAFNPCEDI MGYDFLRVLI WLINILAIMG NMTVLFVLLT SRYKLTVPRF LMCNLSFADF CMGL YLLLI ASVDSQTKGQ YYNHAIDWQT GSGCSTAGFF TVFASELSVY TLTVITLERW HTITYAIHLD QKLRLRHAIL IMLGG WLFS SLIAMLPLVG VSNYMKVSIC FPMDVETTLS QVYILTILIL NVVAFFIICA CYIKIYFAVR NPELMATNKD TKIAKK MAI LIFTDFTCMA PISFFAISAA FKVPLITVTN SKVLLVLFYP INSCANPFLY AIFTKTFQRD FFLLLSKFGC CKRRAEL YR RKDFSAYTSN CKNGFTGSNK PSQSTLKLST LHCQGTALLD KTRYTECHHH HHHHH |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
緩衝液 | pH: 7.4 |
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凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 平均電子線量: 70.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.8 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 311538 |
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初期 角度割当 | タイプ: RANDOM ASSIGNMENT |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |