+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-31596 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
タイトル | luteinizing hormone/choriogonadotropin receptor(S277I)-chorionic gonadotropin-Gs complex | |||||||||
マップデータ | ||||||||||
試料 |
| |||||||||
キーワード | glycoprotein hormone receptor / luteinizing hormone / chorionic gonadotropin / GPCR / Gs-protein / MEMBRANE PROTEIN | |||||||||
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 / 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 / Thyroxine biosynthesis / Mineralocorticoid biosynthesis / positive regulation of inositol trisphosphate biosynthetic process / Glycoprotein hormones / Hormone ligand-binding receptors / 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 / protein targeting to lysosome / male genitalia development / regulation of signaling receptor activity / 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 / Vasopressin regulates renal water homeostasis via Aquaporins / G protein-coupled peptide receptor activity / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) 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 / G alpha (i) signalling events / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Adrenaline,noradrenaline inhibits insulin secretion / alkylglycerophosphoethanolamine phosphodiesterase activity / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / Extra-nuclear estrogen signaling / G alpha (z) signalling events / G alpha (s) signalling events / organ growth / G alpha (q) signalling events / photoreceptor outer segment membrane / arachidonate secretion / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / 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 / activation of adenylate cyclase activity / ovarian follicle development / cardiac muscle cell apoptotic process / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / hormone-mediated signaling pathway / positive regulation of calcium-mediated signaling / 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 / Golgi lumen 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / Bos taurus (ウシ) / Lama glama (ラマ) / 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: 3.9 Å | |||||||||
データ登録者 | Duan J / Xu P | |||||||||
資金援助 | 中国, 1件
| |||||||||
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 |
|
-構造の表示
ムービー |
ムービービューア |
---|---|
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_31596.map.gz | 59.8 MB | EMDBマップデータ形式 | |
---|---|---|---|---|
ヘッダ (付随情報) | emd-31596-v30.xml emd-31596.xml | 20.3 KB 20.3 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_31596.png | 56.3 KB | ||
Filedesc metadata | emd-31596.cif.gz | 6.9 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-31596 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-31596 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_31596_validation.pdf.gz | 504.7 KB | 表示 | EMDB検証レポート |
---|---|---|---|---|
文書・詳細版 | emd_31596_full_validation.pdf.gz | 504.3 KB | 表示 | |
XML形式データ | emd_31596_validation.xml.gz | 6 KB | 表示 | |
CIF形式データ | emd_31596_validation.cif.gz | 6.9 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31596 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31596 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
---|---|
「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_31596.map.gz / 形式: CCP4 / 大きさ: 64 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.045 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
|
-添付データ
-試料の構成要素
+全体 : luteinizing hormone/choriogonadotropin receptor(S277I)-chorionic ...
+超分子 #1: luteinizing hormone/choriogonadotropin receptor(S277I)-chorionic ...
+超分子 #2: luteinizing hormone
+超分子 #3: choriogonadotropin receptor
+超分子 #4: chorionic gonadotropin
+超分子 #5: Gs protein
+超分子 #6: antibody
+分子 #1: Engineered guanine nucleotide-binding protein G(s) subunit alpha
+分子 #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+分子 #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+分子 #4: Camelid antibody VHH fragment Nb35
+分子 #5: Lutropin-choriogonadotropic hormone receptor
+分子 #6: Glycoprotein hormones alpha chain
+分子 #7: Choriogonadotropin subunit beta 3
+分子 #8: 2-acetamido-2-deoxy-beta-D-glucopyranose
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
---|---|
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 |
---|---|
凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
---|---|
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
初期モデル | モデルのタイプ: NONE |
---|---|
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.9 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 355345 |
初期 角度割当 | タイプ: RANDOM ASSIGNMENT |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |