+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8tma | ||||||
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タイトル | Antibody N3-1 bound to RBD in the up conformation | ||||||
要素 |
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キーワード | VIRAL PROTEIN/IMMUNE SYSTEM (ウイルス性) / SARS-CoV-2 spike / neutralizing antibody (中和抗体) / RBD-directed antibody / quaternary epitope / VIRAL PROTEIN (ウイルスタンパク質) / VIRAL PROTEIN-IMMUNE SYSTEM complex (ウイルス性) | ||||||
機能・相同性 | 機能・相同性情報 Maturation of spike protein / viral translation / 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 / structural constituent of virion / host cell endoplasmic reticulum-Golgi intermediate compartment membrane ...Maturation of spike protein / viral translation / 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 / 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 / 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) / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / 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: 3.2 Å | ||||||
データ登録者 | Hsieh, C.-L. / McLellan, J.S. | ||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: Commun Biol / 年: 2023 タイトル: SARS-COV-2 Omicron variants conformationally escape a rare quaternary antibody binding mode. 著者: Jule Goike / Ching-Lin Hsieh / Andrew P Horton / Elizabeth C Gardner / Ling Zhou / Foteini Bartzoka / Nianshuang Wang / Kamyab Javanmardi / Andrew Herbert / Shawn Abbassi / Xuping Xie / ...著者: Jule Goike / Ching-Lin Hsieh / Andrew P Horton / Elizabeth C Gardner / Ling Zhou / Foteini Bartzoka / Nianshuang Wang / Kamyab Javanmardi / Andrew Herbert / Shawn Abbassi / Xuping Xie / Hongjie Xia / Pei-Yong Shi / Rebecca Renberg / Thomas H Segall-Shapiro / Cynthia I Terrace / Wesley Wu / Raghav Shroff / Michelle Byrom / Andrew D Ellington / Edward M Marcotte / James M Musser / Suresh V Kuchipudi / Vivek Kapur / George Georgiou / Scott C Weaver / John M Dye / Daniel R Boutz / Jason S McLellan / Jimmy D Gollihar / 要旨: The ongoing evolution of SARS-CoV-2 into more easily transmissible and infectious variants has provided unprecedented insight into mutations enabling immune escape. Understanding how these mutations ...The ongoing evolution of SARS-CoV-2 into more easily transmissible and infectious variants has provided unprecedented insight into mutations enabling immune escape. Understanding how these mutations affect the dynamics of antibody-antigen interactions is crucial to the development of broadly protective antibodies and vaccines. Here we report the characterization of a potent neutralizing antibody (N3-1) identified from a COVID-19 patient during the first disease wave. Cryogenic electron microscopy revealed a quaternary binding mode that enables direct interactions with all three receptor-binding domains of the spike protein trimer, resulting in extraordinary avidity and potent neutralization of all major variants of concern until the emergence of Omicron. Structure-based rational design of N3-1 mutants improved binding to all Omicron variants but only partially restored neutralization of the conformationally distinct Omicron BA.1. This study provides new insights into immune evasion through changes in spike protein dynamics and highlights considerations for future conformationally biased multivalent vaccine designs. | ||||||
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 | 8tma.cif.gz | 118.5 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8tma.ent.gz | 76.4 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8tma.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/tm/8tma ftp://data.pdbj.org/pub/pdb/validation_reports/tm/8tma | 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: 142427.438 Da / 分子数: 1 / 変異: Hexapro construct / 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: 抗体 | 分子量: 14455.997 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 発現宿主: Homo sapiens (ヒト) |
#3: 抗体 | 分子量: 11828.046 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 発現宿主: Homo sapiens (ヒト) |
-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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由来(天然) |
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由来(組換発現) |
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緩衝液 | pH: 8 / 詳細: 2 mM Tris pH 8.0, 200 mM NaCl, 0.02% NaN3 | ||||||||||||||||||||||||
試料 | 濃度: 0.2 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES 詳細: Collected on UltrAuFoil 1.2-1.3 with 0.2 mg/mL HexaPro and 5x fold molar excess FabN3-1 spiked in 30 minutes before freezing. | ||||||||||||||||||||||||
試料支持 | グリッドの材料: GOLD / グリッドのタイプ: UltrAuFoil R1.2/1.3 | ||||||||||||||||||||||||
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: 295 K |
-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): 2500 nm / 最小 デフォーカス(公称値): 1500 nm |
撮影 | 電子線照射量: 80 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
-解析
CTF補正 | タイプ: NONE | ||||||||||||||||||||||||
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3次元再構成 | 解像度: 3.2 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 266553 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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