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データを開く
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基本情報
| 登録情報 | データベース: PDB / ID: 8jje | ||||||||||||||||||
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| タイトル | RBD of SARS-CoV2 spike protein with ACE2 decoy | ||||||||||||||||||
要素 |
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キーワード | VIRAL PROTEIN/PROTEIN BINDING / SARS-CoV2 / spike protein / ACE2 / ACE2 decoy / VIRAL PROTEIN / VIRAL PROTEIN-PROTEIN BINDING complex | ||||||||||||||||||
| 機能・相同性 | 機能・相同性情報positive regulation of amino acid transport / angiotensin-converting enzyme 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 / positive regulation of gap junction assembly / tryptophan transport / regulation of systemic arterial blood pressure by renin-angiotensin / maternal process involved in female pregnancy / regulation of cardiac conduction ...positive regulation of amino acid transport / angiotensin-converting enzyme 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 / positive regulation of gap junction assembly / tryptophan transport / regulation of systemic arterial blood pressure by renin-angiotensin / maternal process involved in female pregnancy / regulation of cardiac conduction / peptidyl-dipeptidase activity / regulation of vasoconstriction / transporter activator activity / Metabolism of Angiotensinogen to Angiotensins / carboxypeptidase activity / angiotensin maturation / viral life cycle / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / metallocarboxypeptidase activity / positive regulation of cardiac muscle contraction / regulation of cytokine production / blood vessel diameter maintenance / negative regulation of smooth muscle cell proliferation / brush border membrane / negative regulation of ERK1 and ERK2 cascade / positive regulation of reactive oxygen species metabolic process / metallopeptidase activity / endocytic vesicle membrane / regulation of cell population proliferation / virus receptor activity / regulation of inflammatory response / symbiont-mediated disruption of host tissue / Maturation of spike protein / Translation of Structural Proteins / Virion Assembly and Release / endopeptidase activity / host cell surface / host extracellular region / symbiont-mediated-mediated suppression of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / Potential therapeutics for SARS / positive regulation of viral entry into host cell / membrane fusion / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / Attachment and Entry / entry receptor-mediated virion attachment to host cell / receptor-mediated virion attachment to host cell / apical plasma membrane / host cell surface receptor binding / symbiont-mediated suppression of host innate immune response / cilium / membrane raft / endocytosis involved in viral entry into host cell / endoplasmic reticulum lumen / receptor ligand activity / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / symbiont entry into host cell / virion attachment to host cell / host cell plasma membrane / SARS-CoV-2 activates/modulates innate and adaptive immune responses / virion membrane / cell surface / negative regulation of transcription by RNA polymerase II / : / extracellular exosome / extracellular region / zinc ion binding / membrane / identical protein binding / plasma membrane 類似検索 - 分子機能 | ||||||||||||||||||
| 生物種 | Homo sapiens (ヒト)![]() synthetic construct (人工物) | ||||||||||||||||||
| 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: 3.4 Å | ||||||||||||||||||
データ登録者 | Kishikawa, J. / Hirose, M. / Kato, T. / Okamoto, T. | ||||||||||||||||||
| 資金援助 | 日本, 5件
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引用 | ジャーナル: Sci Transl Med / 年: 2023タイトル: An inhaled ACE2 decoy confers protection against SARS-CoV-2 infection in preclinical models. 著者: Emiko Urano / Yumi Itoh / Tatsuya Suzuki / Takanori Sasaki / Jun-Ichi Kishikawa / Kanako Akamatsu / Yusuke Higuchi / Yusuke Sakai / Tomotaka Okamura / Shuya Mitoma / Fuminori Sugihara / Akira ...著者: Emiko Urano / Yumi Itoh / Tatsuya Suzuki / Takanori Sasaki / Jun-Ichi Kishikawa / Kanako Akamatsu / Yusuke Higuchi / Yusuke Sakai / Tomotaka Okamura / Shuya Mitoma / Fuminori Sugihara / Akira Takada / Mari Kimura / Shuto Nakao / Mika Hirose / Tadahiro Sasaki / Ritsuko Koketsu / Shunya Tsuji / Shota Yanagida / Tatsuo Shioda / Eiji Hara / Satoaki Matoba / Yoshiharu Matsuura / Yasunari Kanda / Hisashi Arase / Masato Okada / Junichi Takagi / Takayuki Kato / Atsushi Hoshino / Yasuhiro Yasutomi / Akatsuki Saito / Toru Okamoto / ![]() 要旨: The Omicron variant continuously evolves under the humoral immune pressure exerted by vaccination and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the resulting Omicron ...The Omicron variant continuously evolves under the humoral immune pressure exerted by vaccination and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the resulting Omicron subvariants display further immune evasion and antibody escape. An engineered angiotensin-converting enzyme 2 (ACE2) decoy composed of high-affinity ACE2 and an IgG1 Fc domain could offer an alternative modality to neutralize SARS-CoV-2. We previously reported its broad spectrum and therapeutic potential in rodent models. Here, we demonstrate that the engineered ACE2 decoy retains neutralization activity against Omicron subvariants, including the currently emerging XBB and BQ.1 strains, which completely evade antibodies currently in clinical use. SARS-CoV-2, under the suboptimal concentration of neutralizing drugs, generated SARS-CoV-2 mutants escaping wild-type ACE2 decoy and monoclonal antibodies, whereas no escape mutant emerged against the engineered ACE2 decoy. Furthermore, inhalation of aerosolized decoys improved the outcomes of rodents infected with SARS-CoV-2 at a 20-fold lower dose than that of intravenous administration. Last, the engineered ACE2 decoy exhibited therapeutic efficacy for cynomolgus macaques infected with SARS-CoV-2. These results indicate that this engineered ACE2 decoy represents a promising therapeutic strategy to overcome immune-evading SARS-CoV-2 variants and that liquid aerosol inhalation could be considered as a noninvasive approach to enhance the efficacy of COVID-19 treatments. | ||||||||||||||||||
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構造の表示
| 構造ビューア | 分子: Molmil Jmol/JSmol |
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ダウンロードとリンク
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ダウンロード
| PDBx/mmCIF形式 | 8jje.cif.gz | 210.2 KB | 表示 | PDBx/mmCIF形式 |
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| PDB形式 | pdb8jje.ent.gz | 148.4 KB | 表示 | PDB形式 |
| PDBx/mmJSON形式 | 8jje.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/jj/8jje ftp://data.pdbj.org/pub/pdb/validation_reports/jj/8jje | HTTPS FTP |
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-関連構造データ
| 関連構造データ | ![]() 36345MC 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 ( |
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| 類似構造データ | 類似検索 - 機能・相同性 F&H 検索 |
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リンク
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集合体
| 登録構造単位 | ![]()
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要素
-タンパク質 , 2種, 2分子 AB
| #1: タンパク質 | 分子量: 73198.133 Da / 分子数: 1 / 変異: A25V,K31N,E35K,T92Q,S128C,V343C / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: ACE2, UNQ868/PRO1885 / 細胞株 (発現宿主): Expi293F / 発現宿主: Homo sapiens (ヒト)参照: UniProt: Q9BYF1, angiotensin-converting enzyme 2, 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 |
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| #2: タンパク質 | 分子量: 138621.188 Da / 分子数: 1 / 変異: R682G,R683S,R685G,K986P,V987P / 由来タイプ: 組換発現 詳細: 1-2 is the signal sequence. 1216-1242 is the Trimeric Foldon to from trimeric spike. 1201-1215 and 1243 are the linkers. 1244- is the purification tag. 由来: (組換発現) ![]() 遺伝子: S, 2 / 細胞株 (発現宿主): Expi293F / 発現宿主: Homo sapiens (ヒト) / 株 (発現宿主): Expi293F / 参照: UniProt: P0DTC2 |
-糖 , 5種, 6分子 
| #3: 多糖 | alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2- ...alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | ||||||
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| #4: 多糖 | | #5: 多糖 | alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2- ...alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | #6: 多糖 | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | #7: 糖 | ChemComp-NAG / | |
-非ポリマー , 3種, 3分子 




| #8: 化合物 | ChemComp-ZN / |
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| #9: 化合物 | ChemComp-SO4 / |
| #10: 水 | ChemComp-HOH / |
-詳細
| 研究の焦点であるリガンドがあるか | Y |
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| Has protein modification | Y |
-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 |
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試料調製
| 構成要素 |
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| 分子量 | 値: 0.46 MDa / 実験値: NO | ||||||||||||||||||||||||
| 由来(天然) |
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| 由来(組換発現) |
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| 緩衝液 | pH: 8 | ||||||||||||||||||||||||
| 緩衝液成分 |
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| 試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | ||||||||||||||||||||||||
| 急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 100 % / 凍結前の試料温度: 277 K |
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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 FIELD / 最大 デフォーカス(公称値): 1800 nm / 最小 デフォーカス(公称値): 800 nm / Cs: 0.085 mm / C2レンズ絞り径: 50 µm |
| 試料ホルダ | 凍結剤: NITROGEN 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
| 撮影 | 電子線照射量: 60 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 撮影したグリッド数: 1 / 実像数: 7947 |
| 電子光学装置 | エネルギーフィルター名称: GIF Bioquantum / エネルギーフィルタースリット幅: 20 eV |
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解析
| EMソフトウェア |
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| CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 粒子像の選択 | 選択した粒子像数: 880910 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 対称性 | 点対称性: C1 (非対称) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 3次元再構成 | 解像度: 3.4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 144754 / アルゴリズム: FOURIER SPACE / クラス平均像の数: 1 / 対称性のタイプ: POINT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 精密化 | 解像度: 3.4→3.4 Å / Cor.coef. Fo:Fc: 0.732 / SU B: 19.889 / SU ML: 0.298 / ESU R: 0.467 立体化学のターゲット値: MAXIMUM LIKELIHOOD WITH PHASES 詳細: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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| 溶媒の処理 | 溶媒モデル: PARAMETERS FOR MASK CACLULATION | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 原子変位パラメータ | Biso mean: 116.964 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 精密化ステップ | サイクル: 1 / 合計: 6670 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 拘束条件 |
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コントローラー
万見について




Homo sapiens (ヒト)

日本, 5件
引用









PDBj






FIELD EMISSION GUN