+
データを開く
-
基本情報
登録情報 | データベース: PDB / ID: 8i2h | ||||||
---|---|---|---|---|---|---|---|
タイトル | Follicle stimulating hormone receptor | ||||||
![]() | Follicle-stimulating hormone receptor | ||||||
![]() | HORMONE / FSH / FSHR / GPCR | ||||||
機能・相同性 | ![]() follicle-stimulating hormone receptor activity / regulation of platelet-derived growth factor receptor signaling pathway / regulation of acetylcholine metabolic process / : / regulation of hormone metabolic process / primary ovarian follicle growth / Hormone ligand-binding receptors / follicle-stimulating hormone signaling pathway / female gamete generation / Sertoli cell proliferation ...follicle-stimulating hormone receptor activity / regulation of platelet-derived growth factor receptor signaling pathway / regulation of acetylcholine metabolic process / : / regulation of hormone metabolic process / primary ovarian follicle growth / Hormone ligand-binding receptors / follicle-stimulating hormone signaling pathway / female gamete generation / Sertoli cell proliferation / gonad development / intracellular water homeostasis / sperm DNA condensation / Sertoli cell development / basement membrane organization / transcytosis / cellular response to follicle-stimulating hormone stimulus / regulation of osteoclast differentiation / regulation of systemic arterial blood pressure / female gonad development / G protein-coupled peptide receptor activity / negative regulation of bone resorption / positive regulation of intracellular estrogen receptor signaling pathway / regulation of chromosome organization / uterus development / peptide hormone binding / hormone-mediated signaling pathway / locomotory behavior / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / male gonad development / adenylate cyclase-activating G protein-coupled receptor signaling pathway / neuron projection development / spermatogenesis / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of ERK1 and ERK2 cascade / receptor complex / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / endosome / G protein-coupled receptor signaling pathway / cell surface / membrane / plasma membrane 類似検索 - 分子機能 | ||||||
生物種 | ![]() | ||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 6 Å | ||||||
![]() | Duan, J. / Xu, P. / Yang, J. / Ji, Y. / Zhang, H. / Mao, C. / Luan, X. / Jiang, Y. / Zhang, Y. / Zhang, S. / Xu, H.E. | ||||||
資金援助 | ![]()
| ||||||
![]() | ![]() 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 |
|
-
構造の表示
構造ビューア | 分子: ![]() ![]() |
---|
-
ダウンロードとリンク
-
ダウンロード
PDBx/mmCIF形式 | ![]() | 122.2 KB | 表示 | ![]() |
---|---|---|---|---|
PDB形式 | ![]() | 83 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 977.7 KB | 表示 | ![]() |
---|---|---|---|---|
文書・詳細版 | ![]() | 977.2 KB | 表示 | |
XML形式データ | ![]() | 23.1 KB | 表示 | |
CIF形式データ | ![]() | 33.2 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 35136MC ![]() 8i2gC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 ( |
---|---|
類似構造データ | 類似検索 - 機能・相同性 ![]() |
-
リンク
-
集合体
登録構造単位 | ![]()
|
---|---|
1 |
|
-
要素
#1: タンパク質 | 分子量: 76971.930 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: P23945 |
---|
-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
---|---|
EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-
試料調製
構成要素 | 名称: Follicle stimulating hormone receptor / タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT |
---|---|
由来(天然) | 生物種: ![]() |
由来(組換発現) | 生物種: ![]() ![]() |
緩衝液 | pH: 7.5 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE-PROPANE |
-
電子顕微鏡撮影
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
---|---|
顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: OTHER / 最大 デフォーカス(公称値): 2200 nm / 最小 デフォーカス(公称値): 1200 nm |
撮影 | 電子線照射量: 70 e/Å2 フィルム・検出器のモデル: FEI FALCON IV (4k x 4k) |
-
解析
ソフトウェア | 名称: PHENIX / バージョン: 1.20.1_4487: / 分類: 精密化 | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF補正 | タイプ: NONE | ||||||||||||||||||||||||
3次元再構成 | 解像度: 6 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 356211 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
|