+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-35135 | |||||||||
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タイトル | FSHR-Follicle stimulating hormone-compound 716340-Gs complex | |||||||||
マップデータ | DeepEMhancer sharpen | |||||||||
試料 |
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機能・相同性 | 機能・相同性情報 follicle-stimulating hormone receptor activity / progesterone biosynthetic process / 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 ...follicle-stimulating hormone receptor activity / progesterone biosynthetic process / 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 / Glycoprotein hormones / Hormone ligand-binding receptors / Reactions specific to the complex N-glycan synthesis pathway / Androgen biosynthesis / follicle-stimulating hormone signaling pathway / female gamete generation / Sertoli cell proliferation / gonad development / regulation of protein kinase A signaling / positive regulation of cAMP-mediated signaling / sensory perception of chemical stimulus / negative regulation of organ growth / regulation of osteoclast differentiation / cellular response to follicle-stimulating hormone stimulus / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / regulation of signaling receptor activity / thyroid hormone generation / G protein-coupled peptide receptor activity / beta-2 adrenergic receptor binding / organ growth / female gonad development / PKA activation in glucagon signalling / thyroid gland development / developmental growth / D1 dopamine receptor binding / positive regulation of bone resorption / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway / ionotropic glutamate receptor binding / insulin-like growth factor receptor binding / adenylate cyclase activator activity / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / hormone-mediated signaling pathway / transforming growth factor beta receptor signaling pathway / positive regulation of GTPase activity / female pregnancy / bone development / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-activating G protein-coupled receptor signaling pathway / hormone activity / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / platelet aggregation / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / Golgi lumen / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / male gonad development / G beta:gamma signalling through PI3Kgamma / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / positive regulation of cold-induced thermogenesis / retina development in camera-type eye / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / Lama glama (ラマ) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.8 Å | |||||||||
データ登録者 | Duan J / Xu P / Yang J / Ji Y / Zhang H / Mao C / Luan X / Jiang Y / Zhang Y / Zhang S / Xu HE | |||||||||
資金援助 | 中国, 1件
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引用 | ジャーナル: Nat Commun / 年: 2023 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 |
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-構造の表示
添付画像 |
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-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_35135.map.gz | 55.6 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-35135-v30.xml emd-35135.xml | 27.2 KB 27.2 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_35135.png | 66.7 KB | ||
その他 | emd_35135_additional_1.map.gz emd_35135_additional_2.map.gz emd_35135_half_map_1.map.gz emd_35135_half_map_2.map.gz | 32 MB 59.8 MB 38 MB 38 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-35135 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-35135 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_35135_validation.pdf.gz | 528.9 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_35135_full_validation.pdf.gz | 528.5 KB | 表示 | |
XML形式データ | emd_35135_validation.xml.gz | 11.9 KB | 表示 | |
CIF形式データ | emd_35135_validation.cif.gz | 13.5 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35135 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35135 | HTTPS FTP |
-関連構造データ
関連構造データ | 8i2gMC 8i2hC M: このマップから作成された原子モデル C: 同じ文献を引用 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-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_35135.map.gz / 形式: CCP4 / 大きさ: 64 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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注釈 | DeepEMhancer sharpen | ||||||||||||||||||||||||||||||||||||
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: 1.03 Å | ||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-追加マップ: Locel map on FSH and FSHR-ECD
ファイル | emd_35135_additional_1.map | ||||||||||||
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注釈 | Locel map on FSH and FSHR-ECD | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: b-factor sharpen
ファイル | emd_35135_additional_2.map | ||||||||||||
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注釈 | b-factor sharpen | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_35135_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #2
ファイル | emd_35135_half_map_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
+全体 : FSHR-Follicle stimulating hormone-compound 716340-Gs complex
+超分子 #1: FSHR-Follicle stimulating hormone-compound 716340-Gs complex
+分子 #1: chimera of 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: Nb35
+分子 #5: Follicle-stimulating hormone receptor
+分子 #6: Glycoprotein hormones alpha chain
+分子 #7: Follitropin subunit beta
+分子 #9: CHOLESTEROL
+分子 #10: PALMITIC ACID
+分子 #11: MYRISTIC ACID
+分子 #12: 2-acetamido-2-deoxy-beta-D-glucopyranose
+分子 #13: N-tert-butyl-N-ethyl-8-methoxy-9-propan-2-yloxy-1-thiophen-2-yl-5...
-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: 7.5 |
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凍結 | 凍結剤: ETHANE-PROPANE |
-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: FEI FALCON IV (4k x 4k) 平均電子線量: 50.0 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: OTHER / 撮影モード: OTHER / 最大 デフォーカス(公称値): 2.0 µm / 最小 デフォーカス(公称値): 0.8 µm |
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: 2.8 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 477950 |
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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 |