+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-24733 | |||||||||
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タイトル | Oxytocin receptor (OTR) bound to oxytocin in complex with a heterotrimeric Gq protein | |||||||||
マップデータ | Combined map from local refinements | |||||||||
試料 |
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キーワード | HORMONE / GPCR COMPLEX / TRANSMEMBRANE RECEPTOR / OXYTOCIN RECEPTOR / OTR / OT / OXTR / G PROTEIN / OXYTOCIN / VASOTOCIN / MEMBRANE PROTEIN / MEMBRANE PROTEIN-NEUROPEPTIDE complex | |||||||||
機能・相同性 | 機能・相同性情報 oxytocin receptor activity / positive regulation of hindgut contraction / maternal aggressive behavior / response to anoxia / oxytocin receptor binding / neurohypophyseal hormone activity / V1A vasopressin receptor binding / Vasopressin-like receptors / regulation of systemic arterial blood pressure by vasopressin / vasopressin receptor activity ...oxytocin receptor activity / positive regulation of hindgut contraction / maternal aggressive behavior / response to anoxia / oxytocin receptor binding / neurohypophyseal hormone activity / V1A vasopressin receptor binding / Vasopressin-like receptors / regulation of systemic arterial blood pressure by vasopressin / vasopressin receptor activity / response to prostaglandin E / positive regulation of uterine smooth muscle contraction / maternal process involved in parturition / positive regulation of penile erection / positive regulation of norepinephrine secretion / negative regulation of urine volume / sperm ejaculation / telencephalon development / drinking behavior / grooming behavior / response to sucrose / positive regulation of prostaglandin secretion / response to ether / positive regulation of blood pressure / neuropeptide hormone activity / maternal behavior / digestive tract development / positive regulation of ossification / positive regulation of synapse assembly / positive regulation of female receptivity / response to food / eating behavior / male mating behavior / suckling behavior / microvillus / peptide hormone binding / social behavior / estrous cycle / positive regulation of synaptic transmission / response to electrical stimulus / response to retinoic acid / response to glucocorticoid / cellular response to hormone stimulus / positive regulation of vasoconstriction / muscle contraction / response to cAMP / negative regulation of blood pressure / lactation / response to amphetamine / ERK1 and ERK2 cascade / regulation of heart rate / positive regulation of synaptic transmission, glutamatergic / response to cytokine / secretory granule / response to cocaine / response to activity / response to progesterone / positive regulation of synaptic transmission, GABAergic / female pregnancy / adherens junction / peptide binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / terminal bouton / 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 / memory / Prostacyclin signalling through prostacyclin receptor / response to peptide hormone / 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 / 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 / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / 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 / 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 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / Mus musculus (ハツカネズミ) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.9 Å | |||||||||
データ登録者 | Meyerowitz JG / Panova O / Skiniotis G | |||||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: Nat Struct Mol Biol / 年: 2022 タイトル: The oxytocin signaling complex reveals a molecular switch for cation dependence. 著者: Justin G Meyerowitz / Michael J Robertson / Ximena Barros-Álvarez / Ouliana Panova / Robert M Nwokonko / Yang Gao / Georgios Skiniotis / 要旨: Oxytocin (OT) and vasopressin (AVP) are conserved peptide signaling hormones that are critical for diverse processes including osmotic homeostasis, reproduction, lactation and social interaction. OT ...Oxytocin (OT) and vasopressin (AVP) are conserved peptide signaling hormones that are critical for diverse processes including osmotic homeostasis, reproduction, lactation and social interaction. OT acts through the oxytocin receptor (OTR), a magnesium-dependent G protein-coupled receptor that is a therapeutic target for treatment of postpartum hemorrhage, dysfunctional labor and autism. However, the molecular mechanisms that underlie OTR activation by OT and the dependence on magnesium remain unknown. Here we present the wild-type active-state structure of human OTR bound to OT and miniG determined by cryo-EM. The structure reveals a unique activation mechanism adopted by OTR involving both the formation of a Mg coordination complex between OT and the receptor, and disruption of transmembrane helix 7 (TM7) by OT. Our functional assays demonstrate the role of TM7 disruption and provide the mechanism of full agonism by OT and partial agonism by OT analogs. Furthermore, we find that the identity of a single cation-coordinating residue across vasopressin family receptors determines whether the receptor is cation-dependent. Collectively, these results demonstrate how the Mg-dependent OTR is activated by OT, provide essential information for structure-based drug discovery efforts and shed light on the molecular determinants of cation dependence of vasopressin family receptors throughout the animal kingdom. | |||||||||
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_24733.map.gz | 1.5 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-24733-v30.xml emd-24733.xml | 24.5 KB 24.5 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_24733.png | 156.3 KB | ||
Filedesc metadata | emd-24733.cif.gz | 7 KB | ||
その他 | emd_24733_additional_1.map.gz emd_24733_additional_2.map.gz emd_24733_additional_3.map.gz | 106.6 MB 117.6 MB 117.8 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-24733 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-24733 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_24733_validation.pdf.gz | 345.7 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_24733_full_validation.pdf.gz | 345.3 KB | 表示 | |
XML形式データ | emd_24733_validation.xml.gz | 6.4 KB | 表示 | |
CIF形式データ | emd_24733_validation.cif.gz | 7.4 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24733 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24733 | HTTPS FTP |
-関連構造データ
関連構造データ | 7rycMC 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 | |
電子顕微鏡画像生データ | EMPIAR-10936 (タイトル: Oxytocin receptor (OTR) bound to oxytocin in complex with a heterotrimeric Gq protein Data size: 4.1 TB Data #1: Unaligned multi-frame micrographs of the oxytocin-oxytocin receptor-miniGq complex [micrographs - multiframe]) |
-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_24733.map.gz / 形式: CCP4 / 大きさ: 125 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Combined map from local refinements | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: 0.8521 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
-追加マップ: Local refinement of TMs with deepEMhancer sharpening
ファイル | emd_24733_additional_1.map | ||||||||||||
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注釈 | Local refinement of TMs with deepEMhancer sharpening | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: Local refinement of G protein
ファイル | emd_24733_additional_2.map | ||||||||||||
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注釈 | Local refinement of G protein | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: Global non-uniform refinement
ファイル | emd_24733_additional_3.map | ||||||||||||
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注釈 | Global non-uniform refinement | ||||||||||||
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 : Oxytocin receptor signaling complex with oxytocin and miniGq and ...
+超分子 #1: Oxytocin receptor signaling complex with oxytocin and miniGq and ...
+超分子 #2: Oxytocin
+超分子 #3: Oxytocin receptor
+超分子 #4: miniGq
+超分子 #5: scFv16
+分子 #1: Oxytocin
+分子 #2: Oxytocin receptor
+分子 #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2...
+分子 #4: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+分子 #5: scFv16
+分子 #6: MAGNESIUM ION
-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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グリッド | モデル: UltrAuFoil R1.2/1.3 / 材質: GOLD / 支持フィルム - 材質: GOLD / 支持フィルム - トポロジー: HOLEY / 前処理 - タイプ: GLOW DISCHARGE |
凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | TFS KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 撮影したグリッド数: 1 / 実像数: 40 / 平均露光時間: 2.497 sec. / 平均電子線量: 54.8 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | C2レンズ絞り径: 70.0 µm / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm 最大 デフォーカス(公称値): -0.0018000000000000002 µm 最小 デフォーカス(公称値): -0.0008 µm |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
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: OTHER / 詳細: Ab initio reconstruction |
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最終 再構成 | アルゴリズム: FOURIER SPACE / 解像度のタイプ: BY AUTHOR / 解像度: 2.9 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 423703 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
-原子モデル構築 1
精密化 | 空間: REAL / 温度因子: 69.03 |
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得られたモデル | PDB-7ryc: |