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データを開く
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基本情報
登録情報 | ![]() | |||||||||
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タイトル | CryoEM structure of the HCMV Pentamer gH/gL/UL128/UL130/UL131A in complex with NRP2 and neutralizing fabs 8I21 and 13H11 | |||||||||
![]() | Composite map of combined focused refinement maps. Used for model refinements. | |||||||||
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機能・相同性 | ![]() vestibulocochlear nerve structural organization / dorsal root ganglion morphogenesis / ventral trunk neural crest cell migration / sympathetic neuron projection guidance / facioacoustic ganglion development / trigeminal ganglion development / trigeminal nerve structural organization / sensory neuron axon guidance / facial nerve structural organization / gonadotrophin-releasing hormone neuronal migration to the hypothalamus ...vestibulocochlear nerve structural organization / dorsal root ganglion morphogenesis / ventral trunk neural crest cell migration / sympathetic neuron projection guidance / facioacoustic ganglion development / trigeminal ganglion development / trigeminal nerve structural organization / sensory neuron axon guidance / facial nerve structural organization / gonadotrophin-releasing hormone neuronal migration to the hypothalamus / branchiomotor neuron axon guidance / axon extension involved in axon guidance / sympathetic neuron projection extension / NrCAM interactions / Neurophilin interactions with VEGF and VEGFR / sympathetic ganglion development / neural crest cell migration involved in autonomic nervous system development / vascular endothelial growth factor receptor activity / nerve development / semaphorin receptor complex / outflow tract septum morphogenesis / semaphorin receptor activity / regulation of postsynapse organization / negative chemotaxis / growth factor binding / cytokine binding / semaphorin-plexin signaling pathway / positive regulation of endothelial cell proliferation / positive regulation of endothelial cell migration / cellular response to leukemia inhibitory factor / axon guidance / signaling receptor activity / heparin binding / host cell endosome / host cell Golgi apparatus / postsynaptic membrane / angiogenesis / entry receptor-mediated virion attachment to host cell / cell adhesion / symbiont entry into host cell / fusion of virus membrane with host plasma membrane / axon / viral envelope / glutamatergic synapse / host cell plasma membrane / virion membrane / extracellular region / identical protein binding / membrane / metal ion binding / plasma membrane 類似検索 - 分子機能 | |||||||||
生物種 | ![]() ![]() ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.1 Å | |||||||||
![]() | Kschonsak M / Johnson MC / Schelling R / Green EM / Rouge L / Ho H / Patel N / Kilic C / Kraft E / Arthur CP ...Kschonsak M / Johnson MC / Schelling R / Green EM / Rouge L / Ho H / Patel N / Kilic C / Kraft E / Arthur CP / Rohou AL / Comps-Agrar L / Martinez-Martin N / Perez L / Payandeh J / Ciferri C | |||||||||
資金援助 | 1件
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![]() | ![]() タイトル: Structural basis for HCMV Pentamer receptor recognition and antibody neutralization. 著者: Marc Kschonsak / Matthew C Johnson / Rachel Schelling / Evan M Green / Lionel Rougé / Hoangdung Ho / Nidhi Patel / Cem Kilic / Edward Kraft / Christopher P Arthur / Alexis L Rohou / Laetitia ...著者: Marc Kschonsak / Matthew C Johnson / Rachel Schelling / Evan M Green / Lionel Rougé / Hoangdung Ho / Nidhi Patel / Cem Kilic / Edward Kraft / Christopher P Arthur / Alexis L Rohou / Laetitia Comps-Agrar / Nadia Martinez-Martin / Laurent Perez / Jian Payandeh / Claudio Ciferri / ![]() ![]() 要旨: Human cytomegalovirus (HCMV) represents the viral leading cause of congenital birth defects and uses the gH/gL/UL128-130-131A complex (Pentamer) to enter different cell types, including epithelial ...Human cytomegalovirus (HCMV) represents the viral leading cause of congenital birth defects and uses the gH/gL/UL128-130-131A complex (Pentamer) to enter different cell types, including epithelial and endothelial cells. Upon infection, Pentamer elicits the most potent neutralizing response against HCMV, representing a key vaccine candidate. Despite its relevance, the structural basis for Pentamer receptor recognition and antibody neutralization is largely unknown. Here, we determine the structures of Pentamer bound to neuropilin 2 (NRP2) and a set of potent neutralizing antibodies against HCMV. Moreover, we identify thrombomodulin (THBD) as a functional HCMV receptor and determine the structures of the Pentamer-THBD complex. Unexpectedly, both NRP2 and THBD also promote dimerization of Pentamer. Our results provide a framework for understanding HCMV receptor engagement, cell entry, antibody neutralization, and outline strategies for antiviral therapies against HCMV. | |||||||||
履歴 |
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構造の表示
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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 | ![]() | 2.3 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 55.4 KB 55.4 KB | 表示 表示 | ![]() |
画像 | ![]() | 45 KB | ||
その他 | ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() | 77.5 MB 77.5 MB 22.5 MB 1.2 MB 840.1 KB 77.5 MB 22.5 MB 22.5 MB 22.5 MB 77.6 MB 22.5 MB 22.5 MB 2.2 MB | ||
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 | ![]() 7t4sMC ![]() 7t4qC ![]() 7t4rC 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 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||
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注釈 | Composite map of combined focused refinement maps. Used for model refinements. | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.3514 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: Non-sharpened, full map of overall (non-focused)refinement
+追加マップ: Non-sharpened, full map of focused refinement on 8I21-UL128 region
+追加マップ: Half map 1 of focused refinement on 8I21-UL128 region
+追加マップ: Density modified map of focused refined 8I12-UL128 region....
+追加マップ: Density modified map of focused refined NRP2-UL region....
+追加マップ: Non-sharpened, full map of focused refinement on NRP2-UL region
+追加マップ: Half map 1 of focused refinement on NRP2-UL region
+追加マップ: Half map 2 of focused refinement on NRP2-UL region
+追加マップ: Half map 2 of focused refinement on 8I21-UL128 region
+追加マップ: Non-sharpened, full map of focused refinement on 13H11-gH region
+追加マップ: Half map 1 of focused refinement on 13H11-gH region
+追加マップ: Half map 2 of focused refinement on 13H11-gH region
+追加マップ: Density modified map of focused refined 13H11-gH region....
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試料の構成要素
+全体 : Pentameric complex of HCMV proteins gH, gL, UL128, UL130, UL131A ...
+超分子 #1: Pentameric complex of HCMV proteins gH, gL, UL128, UL130, UL131A ...
+分子 #1: Envelope glycoprotein H
+分子 #2: Envelope glycoprotein L
+分子 #3: Envelope protein UL128
+分子 #4: Envelope glycoprotein UL130
+分子 #5: Envelope protein UL131A
+分子 #6: Neuropilin-2
+分子 #7: Fab 8I21 heavy chain
+分子 #8: Fab 13H11 heavy chain
+分子 #9: Fab 13H11 light chain
+分子 #10: Fab 8I21 light chain
+分子 #11: 2-acetamido-2-deoxy-beta-D-glucopyranose
+分子 #12: CALCIUM 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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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
濃度 | 1 mg/mL | |||||||||
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緩衝液 | pH: 7.5 構成要素:
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グリッド | モデル: UltrAuFoil R0.6/1 / 材質: GOLD / メッシュ: 300 / 前処理 - タイプ: PLASMA CLEANING | |||||||||
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 277.15 K / 装置: LEICA EM GP / 詳細: blot for 3.5 seconds before plunging. | |||||||||
詳細 | Sample was mildly crosslinked with 0.025% glutaraldehyde, incubated for 10 min at room temperature and quenched with 9 mM TRIS pH 7.5 |
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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 K2 SUMMIT (4k x 4k) 検出モード: COUNTING / 撮影したグリッド数: 4 / 実像数: 21357 / 平均露光時間: 10.0 sec. / 平均電子線量: 52.0 e/Å2 詳細: Images were collected in movie-mode at 4 frames/second. |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 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): 1.5 µm / 最小 デフォーカス(公称値): 0.5 µm / 倍率(公称値): 165000 |
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 |