+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8aqw | ||||||
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タイトル | BA.4/5 SARS-CoV-2 Spike bound to mouse ACE2 (local) | ||||||
要素 |
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キーワード | VIRAL PROTEIN (ウイルスタンパク質) / SARS-COV2 (SARSコロナウイルス2) / omicron (Ο) / Spike / RBD / mouse / ACE2 (アンジオテンシン変換酵素2) / ANTIVIRAL PROTEIN / BA4/5 | ||||||
機能・相同性 | 機能・相同性情報 Metabolism of Angiotensinogen to Angiotensins / Fc-gamma receptor I complex binding / immunoglobulin complex, circulating / IgG immunoglobulin complex / immunoglobulin receptor binding / positive regulation of amino acid transport / アンジオテンシン変換酵素2 / positive regulation of L-proline import across plasma membrane / 加水分解酵素; プロテアーゼ; ペプチド結合加水分解酵素; 金属プロテアーゼ / angiotensin-mediated drinking behavior ...Metabolism of Angiotensinogen to Angiotensins / Fc-gamma receptor I complex binding / immunoglobulin complex, circulating / IgG immunoglobulin complex / immunoglobulin receptor binding / positive regulation of amino acid transport / アンジオテンシン変換酵素2 / positive regulation of L-proline import across plasma membrane / 加水分解酵素; プロテアーゼ; ペプチド結合加水分解酵素; 金属プロテアーゼ / angiotensin-mediated drinking behavior / tryptophan transport / positive regulation of gap junction assembly / regulation of systemic arterial blood pressure by renin-angiotensin / regulation of cardiac conduction / peptidyl-dipeptidase activity / maternal process involved in female pregnancy / metallocarboxypeptidase activity / complement activation, classical pathway / carboxypeptidase activity / positive regulation of cardiac muscle contraction / antigen binding / virion component / brush border membrane / negative regulation of smooth muscle cell proliferation / 繊毛 / negative regulation of ERK1 and ERK2 cascade / metallopeptidase activity / virus receptor activity / antibacterial humoral response / Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / endopeptidase activity / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / membrane fusion / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / host cell surface receptor binding / symbiont entry into host cell / apical plasma membrane / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / エンベロープ (ウイルス) / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / 細胞膜 / タンパク質分解 / extracellular space / extracellular region / 生体膜 / identical protein binding / metal ion binding / 細胞膜 / 細胞質 類似検索 - 分子機能 | ||||||
生物種 | Severe acute respiratory syndrome coronavirus 2 (SARSコロナウイルス2) Enterobacteria phage T4 (ファージ) Mus musculus (ハツカネズミ) | ||||||
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: 3.3 Å | ||||||
データ登録者 | Lau, K. / Ni, D. / Beckert, B. / Nazarov, S. / Myasnikov, A. / Pojer, F. / Stahlberg, H. / Uchikawa, E. | ||||||
資金援助 | スイス, 1件
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引用 | ジャーナル: PLoS Pathog / 年: 2023 タイトル: Cryo-EM structures and binding of mouse and human ACE2 to SARS-CoV-2 variants of concern indicate that mutations enabling immune escape could expand host range. 著者: Dongchun Ni / Priscilla Turelli / Bertrand Beckert / Sergey Nazarov / Emiko Uchikawa / Alexander Myasnikov / Florence Pojer / Didier Trono / Henning Stahlberg / Kelvin Lau / 要旨: Investigation of potential hosts of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is crucial to understanding future risks of spillover and spillback. SARS-CoV-2 has been reported ...Investigation of potential hosts of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is crucial to understanding future risks of spillover and spillback. SARS-CoV-2 has been reported to be transmitted from humans to various animals after requiring relatively few mutations. There is significant interest in describing how the virus interacts with mice as they are well adapted to human environments, are used widely as infection models and can be infected. Structural and binding data of the mouse ACE2 receptor with the Spike protein of newly identified SARS-CoV-2 variants are needed to better understand the impact of immune system evading mutations present in variants of concern (VOC). Previous studies have developed mouse-adapted variants and identified residues critical for binding to heterologous ACE2 receptors. Here we report the cryo-EM structures of mouse ACE2 bound to trimeric Spike ectodomains of four different VOC: Beta, Omicron BA.1, Omicron BA.2.12.1 and Omicron BA.4/5. These variants represent the oldest to the newest variants known to bind the mouse ACE2 receptor. Our high-resolution structural data complemented with bio-layer interferometry (BLI) binding assays reveal a requirement for a combination of mutations in the Spike protein that enable binding to the mouse ACE2 receptor. #1: ジャーナル: Biorxiv / 年: 2023 タイトル: Cryo-EM structures and binding of mouse and human ACE2 to SARS-CoV-2 variants of concern indicate that mutations enabling immune escape could expand host range 著者: Ni, D. / Turelli, P. / Beckert, B. / Nazarov, S. / Uchikawa, E. / Myasnikov, A. / Pojer, F. / Trono, D. / Stahlberg, H. / Lau, K. | ||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 8aqw.cif.gz | 189 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8aqw.ent.gz | 132.3 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8aqw.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/aq/8aqw ftp://data.pdbj.org/pub/pdb/validation_reports/aq/8aqw | HTTPS FTP |
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-関連構造データ
関連構造データ | 15592MC 8aqsC 8aqtC 8aquC 8aqvC 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 (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
-集合体
登録構造単位 |
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1 |
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-要素
#1: タンパク質 | 分子量: 142143.391 Da / 分子数: 1 / 由来タイプ: 組換発現 由来: (組換発現) Severe acute respiratory syndrome coronavirus 2 (SARSコロナウイルス2), (組換発現) Enterobacteria phage T4 (ファージ) 遺伝子: S, 2, wac 発現宿主: Cricetulus griseus (モンゴルキヌゲネズミ) 参照: UniProt: P0DTC2, UniProt: P10104 |
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#2: タンパク質 | 分子量: 101733.969 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Mus musculus (ハツカネズミ) / 遺伝子: Ace2, Ighg 発現宿主: Cricetulus griseus (モンゴルキヌゲネズミ) 参照: UniProt: Q8R0I0, UniProt: P01863 |
#3: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose |
#4: 糖 | ChemComp-NAG / |
研究の焦点であるリガンドがあるか | N |
-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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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 |
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分子量 | 値: 0.43 MDa / 実験値: YES | ||||||||||||||||||||||||
由来(天然) |
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由来(組換発現) |
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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 / 詳細: BA.4/5 SARS-CoV-2 Spike bound to mouse ACE2 | ||||||||||||||||||||||||
急速凍結 | 凍結剤: ETHANE |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELDBright-field microscopy / 最大 デフォーカス(公称値): 2800 nm / 最小 デフォーカス(公称値): 800 nm |
撮影 | 電子線照射量: 58 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: dev_4827: / 分類: 精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: NONE | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 103496 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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