+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7r7n | ||||||
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タイトル | SARS-CoV-2 spike in complex with the S2D106 neutralizing antibody Fab fragment (local refinement of the RBD and S2D106) | ||||||
要素 |
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キーワード | VIRAL PROTEIN/IMMUNE SYSTEM / SARS-CoV-2 / COVID-19 / spike glycoprotein / fusion protein / neutralizing antibodies / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID / Inhibitor / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex | ||||||
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 / entry receptor-mediated virion attachment to host cell ...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 / entry receptor-mediated virion attachment to host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / receptor-mediated endocytosis of virus by host cell / membrane fusion / Attachment and Entry / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / symbiont-mediated suppression of host innate immune response / host cell surface receptor binding / 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 / identical protein binding / membrane / plasma membrane 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) Severe acute respiratory syndrome coronavirus 2 (ウイルス) | ||||||
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: 3.95 Å | ||||||
データ登録者 | Park, Y.J. / Veesler, D. / Seattle Structural Genomics Center for Infectious Disease (SSGCID) | ||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: Nature / 年: 2021 タイトル: SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape. 著者: Tyler N Starr / Nadine Czudnochowski / Zhuoming Liu / Fabrizia Zatta / Young-Jun Park / Amin Addetia / Dora Pinto / Martina Beltramello / Patrick Hernandez / Allison J Greaney / Roberta Marzi ...著者: Tyler N Starr / Nadine Czudnochowski / Zhuoming Liu / Fabrizia Zatta / Young-Jun Park / Amin Addetia / Dora Pinto / Martina Beltramello / Patrick Hernandez / Allison J Greaney / Roberta Marzi / William G Glass / Ivy Zhang / Adam S Dingens / John E Bowen / M Alejandra Tortorici / Alexandra C Walls / Jason A Wojcechowskyj / Anna De Marco / Laura E Rosen / Jiayi Zhou / Martin Montiel-Ruiz / Hannah Kaiser / Josh R Dillen / Heather Tucker / Jessica Bassi / Chiara Silacci-Fregni / Michael P Housley / Julia di Iulio / Gloria Lombardo / Maria Agostini / Nicole Sprugasci / Katja Culap / Stefano Jaconi / Marcel Meury / Exequiel Dellota / Rana Abdelnabi / Shi-Yan Caroline Foo / Elisabetta Cameroni / Spencer Stumpf / Tristan I Croll / Jay C Nix / Colin Havenar-Daughton / Luca Piccoli / Fabio Benigni / Johan Neyts / Amalio Telenti / Florian A Lempp / Matteo S Pizzuto / John D Chodera / Christy M Hebner / Herbert W Virgin / Sean P J Whelan / David Veesler / Davide Corti / Jesse D Bloom / Gyorgy Snell / 要旨: An ideal therapeutic anti-SARS-CoV-2 antibody would resist viral escape, have activity against diverse sarbecoviruses, and be highly protective through viral neutralization and effector functions. ...An ideal therapeutic anti-SARS-CoV-2 antibody would resist viral escape, have activity against diverse sarbecoviruses, and be highly protective through viral neutralization and effector functions. Understanding how these properties relate to each other and vary across epitopes would aid the development of therapeutic antibodies and guide vaccine design. Here we comprehensively characterize escape, breadth and potency across a panel of SARS-CoV-2 antibodies targeting the receptor-binding domain (RBD). Despite a trade-off between in vitro neutralization potency and breadth of sarbecovirus binding, we identify neutralizing antibodies with exceptional sarbecovirus breadth and a corresponding resistance to SARS-CoV-2 escape. One of these antibodies, S2H97, binds with high affinity across all sarbecovirus clades to a cryptic epitope and prophylactically protects hamsters from viral challenge. Antibodies that target the angiotensin-converting enzyme 2 (ACE2) receptor-binding motif (RBM) typically have poor breadth and are readily escaped by mutations despite high neutralization potency. Nevertheless, we also characterize a potent RBM antibody (S2E12) with breadth across sarbecoviruses related to SARS-CoV-2 and a high barrier to viral escape. These data highlight principles underlying variation in escape, breadth and potency among antibodies that target the RBD, and identify epitopes and features to prioritize for therapeutic development against the current and potential future pandemics. | ||||||
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 | 7r7n.cif.gz | 104 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7r7n.ent.gz | 68.6 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7r7n.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
文書・要旨 | 7r7n_validation.pdf.gz | 1.2 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7r7n_full_validation.pdf.gz | 1.2 MB | 表示 | |
XML形式データ | 7r7n_validation.xml.gz | 27.2 KB | 表示 | |
CIF形式データ | 7r7n_validation.cif.gz | 35.9 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/r7/7r7n ftp://data.pdbj.org/pub/pdb/validation_reports/r7/7r7n | HTTPS FTP |
-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: 抗体 | 分子量: 13420.936 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) |
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#2: タンパク質 | 分子量: 142427.438 Da / 分子数: 1 / 由来タイプ: 組換発現 由来: (組換発現) Severe acute respiratory syndrome coronavirus 2 (ウイルス) 遺伝子: S, 2 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P0DTC2 |
#3: 抗体 | 分子量: 11569.798 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) |
#4: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta- ...2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose |
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 |
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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 | ||||||||||||||||||||||||
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 FIELD |
撮影 | 電子線照射量: 70 e/Å2 / 検出モード: SUPER-RESOLUTION フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
-解析
EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||
対称性 | 点対称性: C1 (非対称) | |||||||||
3次元再構成 | 解像度: 3.95 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 87587 / 対称性のタイプ: POINT |