+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-33772 | |||||||||
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タイトル | SARS-CoV-2 Spike (6P) in complex with 3 R1-32 Fabs and 3 ACE2 | |||||||||
マップデータ | ||||||||||
試料 |
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キーワード | ACE2 / VIRAL PROTEIN-IMMUNE SYSTEM 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 / tryptophan transport / regulation of systemic arterial blood pressure by renin-angiotensin / positive regulation of gap junction assembly / regulation of vasoconstriction / 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 / tryptophan transport / regulation of systemic arterial blood pressure by renin-angiotensin / positive regulation of gap junction assembly / regulation of vasoconstriction / regulation of cardiac conduction / peptidyl-dipeptidase activity / maternal process involved in female pregnancy / angiotensin maturation / metallocarboxypeptidase activity / Metabolism of Angiotensinogen to Angiotensins / Attachment and Entry / carboxypeptidase activity / negative regulation of signaling receptor activity / positive regulation of cardiac muscle contraction / regulation of cytokine production / viral life cycle / blood vessel diameter maintenance / brush border membrane / regulation of transmembrane transporter activity / negative regulation of smooth muscle cell proliferation / negative regulation of ERK1 and ERK2 cascade / cilium / metallopeptidase activity / endocytic vesicle membrane / 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 / endopeptidase activity / Translation of Structural Proteins / Virion Assembly and Release / 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 / membrane raft / apical plasma membrane / endoplasmic reticulum lumen / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / cell surface / extracellular space / zinc ion binding / extracellular exosome / extracellular region / identical protein binding / membrane / plasma membrane 類似検索 - 分子機能 | |||||||||
生物種 | Severe acute respiratory syndrome coronavirus 2 (ウイルス) / Homo sapiens (ヒト) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.73 Å | |||||||||
データ登録者 | Liu B / Gao X / Li Z / Chen X / He J / Chen L / Xiong X | |||||||||
資金援助 | 中国, 1件
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引用 | ジャーナル: Nat Microbiol / 年: 2022 タイトル: SARS-CoV-2 Delta and Omicron variants evade population antibody response by mutations in a single spike epitope. 著者: Ping He / Banghui Liu / Xijie Gao / Qihong Yan / Rongjuan Pei / Jing Sun / Qiuluan Chen / Ruitian Hou / Zimu Li / Yanjun Zhang / Jincun Zhao / Hao Sun / Bo Feng / Qian Wang / Haisu Yi / Peiyu ...著者: Ping He / Banghui Liu / Xijie Gao / Qihong Yan / Rongjuan Pei / Jing Sun / Qiuluan Chen / Ruitian Hou / Zimu Li / Yanjun Zhang / Jincun Zhao / Hao Sun / Bo Feng / Qian Wang / Haisu Yi / Peiyu Hu / Pingchao Li / Yudi Zhang / Zhilong Chen / Xuefeng Niu / Xiaolin Zhong / Liang Jin / Xiaofeng Liu / Kun Qu / Katarzyna A Ciazynska / Andrew P Carter / John A G Briggs / Jizheng Chen / Jinsong Liu / Xinwen Chen / Jun He / Ling Chen / Xiaoli Xiong / 要旨: Population antibody response is thought to be important in selection of virus variants. We report that SARS-CoV-2 infection elicits a population immune response that is mediated by a lineage of VH1- ...Population antibody response is thought to be important in selection of virus variants. We report that SARS-CoV-2 infection elicits a population immune response that is mediated by a lineage of VH1-69 germline antibodies. A representative antibody R1-32 from this lineage was isolated. By cryo-EM, we show that it targets a semi-cryptic epitope in the spike receptor-binding domain. Binding to this non-ACE2 competing epitope results in spike destruction, thereby inhibiting virus entry. On the basis of epitope location, neutralization mechanism and analysis of antibody binding to spike variants, we propose that recurrent substitutions at 452 and 490 are associated with immune evasion of the identified population antibody response. These substitutions, including L452R (present in the Delta variant), disrupt interactions mediated by the VH1-69-specific hydrophobic HCDR2 to impair antibody-antigen association, enabling variants to escape. The first Omicron variants were sensitive to antibody R1-32 but subvariants that harbour L452R quickly emerged and spread. Our results provide insights into how SARS-CoV-2 variants emerge and evade host immune responses. | |||||||||
履歴 |
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-構造の表示
添付画像 |
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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 | emd_33772.map.gz | 96.5 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-33772-v30.xml emd-33772.xml | 23 KB 23 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_33772_fsc.xml | 13.7 KB | 表示 | FSCデータファイル |
画像 | emd_33772.png | 137.6 KB | ||
その他 | emd_33772_half_map_1.map.gz emd_33772_half_map_2.map.gz | 81 MB 81 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-33772 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33772 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_33772_validation.pdf.gz | 883.9 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_33772_full_validation.pdf.gz | 883.5 KB | 表示 | |
XML形式データ | emd_33772_validation.xml.gz | 17.5 KB | 表示 | |
CIF形式データ | emd_33772_validation.cif.gz | 23.2 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33772 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33772 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_33772.map.gz / 形式: CCP4 / 大きさ: 103 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 1.408 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
-ハーフマップ: #1
ファイル | emd_33772_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #2
ファイル | emd_33772_half_map_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
+全体 : SARS-COV-2 Spike_GSAS_6P bound with three R1-32 Fabs and three ACE2
+超分子 #1: SARS-COV-2 Spike_GSAS_6P bound with three R1-32 Fabs and three ACE2
+超分子 #2: SARS-COV-2 Spike_GSAS_6P
+超分子 #3: ACE2
+超分子 #4: Fabs
+分子 #1: Spike glycoprotein
+分子 #2: Angiotensin-converting enzyme 2
+分子 #3: heavy chain of R1-32 Fab
+分子 #4: light chain of R1-32 Fab
+分子 #6: 2-acetamido-2-deoxy-beta-D-glucopyranose
+分子 #7: ZINC 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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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
緩衝液 | pH: 8 |
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凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI TALOS ARCTICA |
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撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 実像数: 6989 / 平均露光時間: 1.6 sec. / 平均電子線量: 63.0 e/Å2 |
電子線 | 加速電圧: 200 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2.5 µm / 最小 デフォーカス(公称値): 0.8 µm / 倍率(公称値): 45000 |
試料ステージ | ホルダー冷却材: NITROGEN |
実験機器 | モデル: Talos Arctica / 画像提供: FEI Company |