+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7fdh | ||||||
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タイトル | SARS-COV-2 Spike RBDMACSp25 binding to hACE2 | ||||||
要素 |
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キーワード | VIRAL PROTEIN (ウイルスタンパク質) / SARS-COV-2 Spike / hACE2 (アンジオテンシン変換酵素2) / mouse-adapted | ||||||
機能・相同性 | 機能・相同性情報 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 vasoconstriction / regulation of cardiac conduction ...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 vasoconstriction / regulation of cardiac conduction / peptidyl-dipeptidase activity / angiotensin maturation / maternal process involved in female pregnancy / Metabolism of Angiotensinogen to Angiotensins / metallocarboxypeptidase activity / Attachment and Entry / carboxypeptidase activity / negative regulation of signaling receptor activity / positive regulation of cardiac muscle contraction / regulation of cytokine production / ウイルスのライフサイクル / blood vessel diameter maintenance / brush border membrane / regulation of transmembrane transporter activity / negative regulation of smooth muscle cell proliferation / 繊毛 / negative regulation of ERK1 and ERK2 cascade / endocytic vesicle membrane / metallopeptidase activity / positive regulation of reactive oxygen species metabolic process / virus receptor activity / regulation of cell population proliferation / regulation of inflammatory response / Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / endopeptidase activity / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / Potential therapeutics for SARS / structural constituent of virion / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / entry receptor-mediated virion attachment to host cell / 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 / 脂質ラフト / apical plasma membrane / fusion of virus membrane with host plasma membrane / 小胞体 / fusion of virus membrane with host endosome membrane / エンベロープ (ウイルス) / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / 細胞膜 / extracellular space / extracellular exosome / zinc ion binding / extracellular region / 生体膜 / identical protein binding / 細胞膜 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) Severe acute respiratory syndrome coronavirus 2 (SARSコロナウイルス2) | ||||||
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: 3.72 Å | ||||||
データ登録者 | Wang, X. / Cao, L. | ||||||
引用 | ジャーナル: Nat Commun / 年: 2021 タイトル: Characterization and structural basis of a lethal mouse-adapted SARS-CoV-2. 著者: Shihui Sun / Hongjing Gu / Lei Cao / Qi Chen / Qing Ye / Guan Yang / Rui-Ting Li / Hang Fan / Yong-Qiang Deng / Xiaopeng Song / Yini Qi / Min Li / Jun Lan / Rui Feng / Yan Guo / Na Zhu / Si ...著者: Shihui Sun / Hongjing Gu / Lei Cao / Qi Chen / Qing Ye / Guan Yang / Rui-Ting Li / Hang Fan / Yong-Qiang Deng / Xiaopeng Song / Yini Qi / Min Li / Jun Lan / Rui Feng / Yan Guo / Na Zhu / Si Qin / Lei Wang / Yi-Fei Zhang / Chao Zhou / Lingna Zhao / Yuehong Chen / Meng Shen / Yujun Cui / Xiao Yang / Xinquan Wang / Wenjie Tan / Hui Wang / Xiangxi Wang / Cheng-Feng Qin / 要旨: There is an urgent need for animal models to study SARS-CoV-2 pathogenicity. Here, we generate and characterize a novel mouse-adapted SARS-CoV-2 strain, MASCp36, that causes severe respiratory ...There is an urgent need for animal models to study SARS-CoV-2 pathogenicity. Here, we generate and characterize a novel mouse-adapted SARS-CoV-2 strain, MASCp36, that causes severe respiratory symptoms, and mortality. Our model exhibits age- and gender-related mortality akin to severe COVID-19. Deep sequencing identified three amino acid substitutions, N501Y, Q493H, and K417N, at the receptor binding domain (RBD) of MASCp36, during in vivo passaging. All three RBD mutations significantly enhance binding affinity to its endogenous receptor, ACE2. Cryo-electron microscopy analysis of human ACE2 (hACE2), or mouse ACE2 (mACE2), in complex with the RBD of MASCp36, at 3.1 to 3.7 Å resolution, reveals the molecular basis for the receptor-binding switch. N501Y and Q493H enhance the binding affinity to hACE2, whereas triple mutations at N501Y/Q493H/K417N decrease affinity and reduce infectivity of MASCp36. Our study provides a platform for studying SARS-CoV-2 pathogenesis, and unveils the molecular mechanism for its rapid adaptation and evolution. | ||||||
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 | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7fdh.cif.gz | 151.4 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7fdh.ent.gz | 122 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7fdh.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/fd/7fdh ftp://data.pdbj.org/pub/pdb/validation_reports/fd/7fdh | HTTPS FTP |
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-関連構造データ
-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: 71828.719 Da / 分子数: 1 / 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 / 発現宿主: Homo sapiens (ヒト) 参照: UniProt: Q9BYF1, アンジオテンシン変換酵素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: 24111.188 Da / 分子数: 1 / Mutation: Q493H, N501Y / 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) 遺伝子: S, 2 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P0DTC2 | ||
#3: 糖 | ChemComp-NAG / 研究の焦点であるリガンドがあるか | 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 |
-試料調製
構成要素 | 名称: SARS-CoV-2 spike RBDMACSp25-hACE2 complex / タイプ: COMPLEX / Entity ID: #1 / 由来: RECOMBINANT |
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由来(天然) | 生物種: Severe acute respiratory syndrome coronavirus 2 (SARSコロナウイルス2) |
由来(組換発現) | 生物種: human (ヒト) |
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 |
急速凍結 | 凍結剤: ETHANE |
-電子顕微鏡撮影
顕微鏡 | モデル: FEI TITAN |
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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 |
撮影 | 電子線照射量: 60 e/Å2 フィルム・検出器のモデル: GATAN K2 BASE (4k x 4k) |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.17.1_3660: / 分類: 精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.72 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 68211 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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