+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7mjn | |||||||||
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タイトル | Cryo-EM structure of the SARS-CoV-2 N501Y mutant spike protein ectodomain bound to human ACE2 ectodomain (focused refinement of RBD and ACE2) | |||||||||
要素 |
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キーワード | VIRAL PROTEIN/Hydrolase (ウイルス性) / SARS-CoV-2 (SARSコロナウイルス2) / glycoprotein (糖タンパク質) / fusion protein (融合タンパク質) / viral protein (ウイルスタンパク質) / ACE2 (アンジオテンシン変換酵素2) / VIRAL PROTEIN-Hydrolase complex (ウイルス性) | |||||||||
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 / regulation of cytokine production / positive regulation of cardiac muscle contraction / ウイルスのライフサイクル / blood vessel diameter maintenance / negative regulation of smooth muscle cell proliferation / regulation of transmembrane transporter activity / brush border membrane / 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 / host cell surface / host extracellular space / endopeptidase activity / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / Potential therapeutics for SARS / 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) / 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 / 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 | Severe acute respiratory syndrome coronavirus 2 (SARSコロナウイルス2) Homo sapiens (ヒト) | |||||||||
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: 3.29 Å | |||||||||
データ登録者 | Zhu, X. / Mannar, D. / Srivastava, S.S. / Berezuk, A.M. / Demers, J.P. / Saville, J.W. / Leopold, K. / Li, W. / Dimitrov, D.S. / Tuttle, K.S. ...Zhu, X. / Mannar, D. / Srivastava, S.S. / Berezuk, A.M. / Demers, J.P. / Saville, J.W. / Leopold, K. / Li, W. / Dimitrov, D.S. / Tuttle, K.S. / Zhou, S. / Chittori, S. / Subramaniam, S. | |||||||||
資金援助 | カナダ, 2件
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引用 | ジャーナル: PLoS Biol / 年: 2021 タイトル: Cryo-electron microscopy structures of the N501Y SARS-CoV-2 spike protein in complex with ACE2 and 2 potent neutralizing antibodies. 著者: Xing Zhu / Dhiraj Mannar / Shanti S Srivastava / Alison M Berezuk / Jean-Philippe Demers / James W Saville / Karoline Leopold / Wei Li / Dimiter S Dimitrov / Katharine S Tuttle / Steven Zhou ...著者: Xing Zhu / Dhiraj Mannar / Shanti S Srivastava / Alison M Berezuk / Jean-Philippe Demers / James W Saville / Karoline Leopold / Wei Li / Dimiter S Dimitrov / Katharine S Tuttle / Steven Zhou / Sagar Chittori / Sriram Subramaniam / 要旨: The recently reported "UK variant" (B.1.1.7) of SARS-CoV-2 is thought to be more infectious than previously circulating strains as a result of several changes, including the N501Y mutation. We ...The recently reported "UK variant" (B.1.1.7) of SARS-CoV-2 is thought to be more infectious than previously circulating strains as a result of several changes, including the N501Y mutation. We present a 2.9-Å resolution cryo-electron microscopy (cryo-EM) structure of the complex between the ACE2 receptor and N501Y spike protein ectodomains that shows Y501 inserted into a cavity at the binding interface near Y41 of ACE2. This additional interaction provides a structural explanation for the increased ACE2 affinity of the N501Y mutant, and likely contributes to its increased infectivity. However, this mutation does not result in large structural changes, enabling important neutralization epitopes to be retained in the spike receptor binding domain. We confirmed this through biophysical assays and by determining cryo-EM structures of spike protein ectodomains bound to 2 representative potent neutralizing antibody fragments. | |||||||||
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 | 7mjn.cif.gz | 179.3 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7mjn.ent.gz | 130.2 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7mjn.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/mj/7mjn ftp://data.pdbj.org/pub/pdb/validation_reports/mj/7mjn | 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: 142476.500 Da / 分子数: 1 / 変異: 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 | ||
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#2: タンパク質 | 分子量: 70386.992 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 | ||
#3: 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 | 名称: SARS-CoV-2 N501Y mutant spike protein ectodomain bound to human ACE2 ectodomain タイプ: COMPLEX / Entity ID: #1-#2 / 由来: MULTIPLE SOURCES |
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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: Homo sapiens (ヒト) |
緩衝液 | pH: 8 |
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
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 |
撮影 | 電子線照射量: 40 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 |
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EMソフトウェア | 名称: cryoSPARC / カテゴリ: 最終オイラー角割当 | ||||||||||||||||||||||||
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.29 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 194473 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
精密化 | 交差検証法: NONE 立体化学のターゲット値: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 150.77 Å2 | ||||||||||||||||||||||||
拘束条件 |
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