+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6wpt | |||||||||
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タイトル | Structure of the SARS-CoV-2 spike glycoprotein in complex with the S309 neutralizing antibody Fab fragment (open state) | |||||||||
要素 |
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キーワード | VIRAL PROTEIN/IMMUNE SYSTEM / SARS-CoV-2 / SARS-CoV / spike glycoprotein / fusion protein / neutralizing antibody / sarbecovirus / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID / 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 / host cell surface receptor binding / symbiont-mediated suppression of host innate immune response / 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 | Severe acute respiratory syndrome coronavirus 2 (ウイルス) 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: 3.7 Å | |||||||||
データ登録者 | Pinto, D. / Park, Y.J. / Beltramello, M. / Walls, A.C. / Tortorici, M.A. / Bianchi, S. / Jaconi, S. / Culap, K. / Zatta, F. / De Marco, A. ...Pinto, D. / Park, Y.J. / Beltramello, M. / Walls, A.C. / Tortorici, M.A. / Bianchi, S. / Jaconi, S. / Culap, K. / Zatta, F. / De Marco, A. / Peter, A. / Guarino, B. / Spreafico, R. / Cameroni, E. / Case, J.B. / Chen, R.E. / Havenar-Daughton, C. / Snell, G. / Virgin, H.W. / Lanzavecchia, A. / Diamond, M.S. / Fink, K. / Veesler, D. / Corti, 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: 2020 タイトル: Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody. 著者: Dora Pinto / Young-Jun Park / Martina Beltramello / Alexandra C Walls / M Alejandra Tortorici / Siro Bianchi / Stefano Jaconi / Katja Culap / Fabrizia Zatta / Anna De Marco / Alessia Peter / ...著者: Dora Pinto / Young-Jun Park / Martina Beltramello / Alexandra C Walls / M Alejandra Tortorici / Siro Bianchi / Stefano Jaconi / Katja Culap / Fabrizia Zatta / Anna De Marco / Alessia Peter / Barbara Guarino / Roberto Spreafico / Elisabetta Cameroni / James Brett Case / Rita E Chen / Colin Havenar-Daughton / Gyorgy Snell / Amalio Telenti / Herbert W Virgin / Antonio Lanzavecchia / Michael S Diamond / Katja Fink / David Veesler / Davide Corti / 要旨: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged coronavirus that is responsible for the current pandemic of coronavirus disease 2019 (COVID-19), which has resulted in ...Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged coronavirus that is responsible for the current pandemic of coronavirus disease 2019 (COVID-19), which has resulted in more than 3.7 million infections and 260,000 deaths as of 6 May 2020. Vaccine and therapeutic discovery efforts are paramount to curb the pandemic spread of this zoonotic virus. The SARS-CoV-2 spike (S) glycoprotein promotes entry into host cells and is the main target of neutralizing antibodies. Here we describe several monoclonal antibodies that target the S glycoprotein of SARS-CoV-2, which we identified from memory B cells of an individual who was infected with severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003. One antibody (named S309) potently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2, by engaging the receptor-binding domain of the S glycoprotein. Using cryo-electron microscopy and binding assays, we show that S309 recognizes an epitope containing a glycan that is conserved within the Sarbecovirus subgenus, without competing with receptor attachment. Antibody cocktails that include S309 in combination with other antibodies that we identified further enhanced SARS-CoV-2 neutralization, and may limit the emergence of neutralization-escape mutants. These results pave the way for using S309 and antibody cocktails containing S309 for prophylaxis in individuals at a high risk of exposure or as a post-exposure therapy to limit or treat severe disease. #1: ジャーナル: bioRxiv / 年: 2020 タイトル: Structural and functional analysis of a potent sarbecovirus neutralizing antibody. 著者: Dora Pinto / Young-Jun Park / Martina Beltramello / Alexandra C Walls / M Alejandra Tortorici / Siro Bianchi / Stefano Jaconi / Katja Culap / Fabrizia Zatta / Anna De Marco / Alessia Peter / ...著者: Dora Pinto / Young-Jun Park / Martina Beltramello / Alexandra C Walls / M Alejandra Tortorici / Siro Bianchi / Stefano Jaconi / Katja Culap / Fabrizia Zatta / Anna De Marco / Alessia Peter / Barbara Guarino / Roberto Spreafico / Elisabetta Cameroni / James Brett Case / Rita E Chen / Colin Havenar-Daughton / Gyorgy Snell / Amalio Telenti / Herbert W Virgin / Antonio Lanzavecchia / Michael S Diamond / Katja Fink / David Veesler / Davide Corti 要旨: SARS-CoV-2 is a newly emerged coronavirus responsible for the current COVID-19 pandemic that has resulted in more than one million infections and 73,000 deaths . Vaccine and therapeutic discovery ...SARS-CoV-2 is a newly emerged coronavirus responsible for the current COVID-19 pandemic that has resulted in more than one million infections and 73,000 deaths . Vaccine and therapeutic discovery efforts are paramount to curb the pandemic spread of this zoonotic virus. The SARS-CoV-2 spike (S) glycoprotein promotes entry into host cells and is the main target of neutralizing antibodies. Here we describe multiple monoclonal antibodies targeting SARS-CoV-2 S identified from memory B cells of a SARS survivor infected in 2003. One antibody, named S309, potently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 by engaging the S receptor-binding domain. Using cryo-electron microscopy and binding assays, we show that S309 recognizes a glycan-containing epitope that is conserved within the sarbecovirus subgenus, without competing with receptor attachment. Antibody cocktails including S309 along with other antibodies identified here further enhanced SARS-CoV-2 neutralization and may limit the emergence of neutralization-escape mutants. These results pave the way for using S309 and S309-containing antibody cocktails for prophylaxis in individuals at high risk of exposure or as a post-exposure therapy to limit or treat severe disease. | |||||||||
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 | 6wpt.cif.gz | 646.1 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6wpt.ent.gz | 499.3 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6wpt.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 | 6wpt_validation.pdf.gz | 3.5 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 6wpt_full_validation.pdf.gz | 3.5 MB | 表示 | |
XML形式データ | 6wpt_validation.xml.gz | 88.3 KB | 表示 | |
CIF形式データ | 6wpt_validation.cif.gz | 137.5 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/wp/6wpt ftp://data.pdbj.org/pub/pdb/validation_reports/wp/6wpt | 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
-タンパク質 , 1種, 3分子 ABC
#1: タンパク質 | 分子量: 141532.797 Da / 分子数: 3 断片: signaling sequence + ectodomain (UNP residues 14-1211) + foldon trimerization domain + TEV cleavage site + His-tag,signaling sequence + ectodomain (UNP residues 14-1211) + foldon ...断片: signaling sequence + ectodomain (UNP residues 14-1211) + foldon trimerization domain + TEV cleavage site + His-tag,signaling sequence + ectodomain (UNP residues 14-1211) + foldon trimerization domain + TEV cleavage site + His-tag 変異: R701S,R702G,R704G,K1005P,V1005P / 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 |
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-抗体 , 2種, 4分子 HDLE
#2: 抗体 | 分子量: 14005.526 Da / 分子数: 2 / 断片: Fab / 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: 11444.677 Da / 分子数: 2 / 断片: Fab / 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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-糖 , 4種, 47分子
#4: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #5: 多糖 | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose | #6: 多糖 | alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2- ...alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose | #7: 糖 | ChemComp-NAG / |
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-詳細
研究の焦点であるリガンドがあるか | Y |
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Has protein modification | 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 |
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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 | ||||||||||||||||||||||||
試料支持 | グリッドの材料: GOLD / グリッドのタイプ: UltrAuFoil | ||||||||||||||||||||||||
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 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: 3.7 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 119608 / 対称性のタイプ: POINT | ||||||||||||||||||
原子モデル構築 | プロトコル: OTHER | ||||||||||||||||||
原子モデル構築 | PDB-ID: 6VXX Accession code: 6VXX / Source name: PDB / タイプ: experimental model | ||||||||||||||||||
精密化 | 最高解像度: 3.7 Å |