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データを開く
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基本情報
登録情報 | データベース: PDB / ID: 7mkm | |||||||||
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タイトル | SARS-CoV-2 Spike RBD in complex with neutralizing Fab SARS2-38 (local refinement) | |||||||||
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![]() | VIRAL PROTEIN/IMMUNE SYSTEM / Glycoprotein / Antibody / VIRAL PROTEIN-IMMUNE SYSTEM complex / Structural Genomics / Center for Structural Genomics of Infectious Diseases / CSGID | |||||||||
機能・相同性 | ![]() 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 / 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 | ![]() ![]() ![]() ![]() | |||||||||
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: 3.16 Å | |||||||||
![]() | Adams, L.J. / Fremont, D.H. / Center for Structural Genomics of Infectious Diseases (CSGID) | |||||||||
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![]() | ![]() タイトル: A potently neutralizing SARS-CoV-2 antibody inhibits variants of concern by utilizing unique binding residues in a highly conserved epitope. 著者: Laura A VanBlargan / Lucas J Adams / Zhuoming Liu / Rita E Chen / Pavlo Gilchuk / Saravanan Raju / Brittany K Smith / Haiyan Zhao / James Brett Case / Emma S Winkler / Bradley M Whitener / ...著者: Laura A VanBlargan / Lucas J Adams / Zhuoming Liu / Rita E Chen / Pavlo Gilchuk / Saravanan Raju / Brittany K Smith / Haiyan Zhao / James Brett Case / Emma S Winkler / Bradley M Whitener / Lindsay Droit / Ishmael D Aziati / Traci L Bricker / Astha Joshi / Pei-Yong Shi / Adrian Creanga / Amarendra Pegu / Scott A Handley / David Wang / Adrianus C M Boon / James E Crowe / Sean P J Whelan / Daved H Fremont / Michael S Diamond / ![]() 要旨: With the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increased transmissibility and potential resistance, antibodies and vaccines with broadly inhibitory ...With the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increased transmissibility and potential resistance, antibodies and vaccines with broadly inhibitory activity are needed. Here, we developed a panel of neutralizing anti-SARS-CoV-2 monoclonal antibodies (mAbs) that bound the receptor binding domain of the spike protein at distinct epitopes and blocked virus attachment to its host receptor, human angiotensin converting enzyme-2 (hACE2). Although several potently neutralizing mAbs protected K18-hACE2 transgenic mice against infection caused by ancestral SARS-CoV-2 strains, others induced escape variants in vivo or lost neutralizing activity against emerging strains. One mAb, SARS2-38, potently neutralized all tested SARS-CoV-2 variants of concern and protected mice against challenge by multiple SARS-CoV-2 strains. Structural analysis showed that SARS2-38 engaged a conserved epitope proximal to the receptor binding motif. Thus, treatment with or induction of neutralizing antibodies that bind conserved spike epitopes may limit the loss of potency of therapies or vaccines against emerging SARS-CoV-2 variants. #1: ジャーナル: bioRxiv / 年: 2021 タイトル: A potently neutralizing anti-SARS-CoV-2 antibody inhibits variants of concern by binding a highly conserved epitope. 著者: Laura VanBlargan / Lucas Adams / Zhuoming Liu / Rita E Chen / Pavlo Gilchuk / Saravanan Raju / Brittany Smith / Haiyan Zhao / James Brett Case / Emma S Winkler / Bradley Whitener / Lindsay ...著者: Laura VanBlargan / Lucas Adams / Zhuoming Liu / Rita E Chen / Pavlo Gilchuk / Saravanan Raju / Brittany Smith / Haiyan Zhao / James Brett Case / Emma S Winkler / Bradley Whitener / Lindsay Droit / Ismael Aziati / Pei-Yong Shi / Adrian Creanga / Amarendra Pegu / Scott Handley / David Wang / Adrianus Boon / James E Crowe / Sean P J Whelan / Daved Fremont / Michael Diamond 要旨: With the emergence of SARS-CoV-2 variants with increased transmissibility and potential resistance, antibodies and vaccines with broadly inhibitory activity are needed. Here we developed a panel of ...With the emergence of SARS-CoV-2 variants with increased transmissibility and potential resistance, antibodies and vaccines with broadly inhibitory activity are needed. Here we developed a panel of neutralizing anti-SARS-CoV-2 mAbs that bind the receptor binding domain of the spike protein at distinct epitopes and block virus attachment to cells and its receptor, human angiotensin converting enzyme-2 (hACE2). While several potently neutralizing mAbs protected K18-hACE2 transgenic mice against infection caused by historical SARS-CoV-2 strains, others induced escape variants in vivo and lost activity against emerging strains. We identified one mAb, SARS2-38, that potently neutralizes all SARS-CoV-2 variants of concern tested and protects mice against challenge by multiple SARS-CoV-2 strains. Structural analysis showed that SARS2-38 engages a conserved epitope proximal to the receptor binding motif. Thus, treatment with or induction of inhibitory antibodies that bind conserved spike epitopes may limit the loss of potency of therapies or vaccines against emerging SARS-CoV-2 variants. | |||||||||
履歴 |
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構造の表示
ムービー |
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構造ビューア | 分子: ![]() ![]() |
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ダウンロードとリンク
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ダウンロード
PDBx/mmCIF形式 | ![]() | 88.2 KB | 表示 | ![]() |
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PDB形式 | ![]() | 67.7 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 683.8 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 687.7 KB | 表示 | |
XML形式データ | ![]() | 24.4 KB | 表示 | |
CIF形式データ | ![]() | 34.5 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
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リンク
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集合体
登録構造単位 | ![]()
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要素
#1: タンパク質 | 分子量: 21247.758 Da / 分子数: 1 / 断片: receptor binding domain (UNP residues 333-520) / 由来タイプ: 組換発現 由来: (組換発現) ![]() ![]() 遺伝子: S, 2 / 細胞株 (発現宿主): Expi293F / 発現宿主: ![]() |
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#2: 抗体 | 分子量: 12490.882 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() ![]() |
#3: 抗体 | 分子量: 11419.787 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() ![]() |
#4: 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 |
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試料調製
構成要素 | 名称: SARS-CoV-2 spike bound by SARS2-38 antibody Fab / タイプ: COMPLEX / Entity ID: #1-#3 / 由来: MULTIPLE SOURCES |
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由来(天然) | 生物種: ![]() ![]() |
緩衝液 | pH: 7.4 |
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 |
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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: ![]() |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 電子線照射量: 50 e/Å2 フィルム・検出器のモデル: FEI FALCON IV (4k x 4k) |
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解析
ソフトウェア | 名称: PHENIX / バージョン: 1.19.2_4158: / 分類: 精密化 | ||||||||||||||||||||||||
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EMソフトウェア | 名称: cryoSPARC / バージョン: 3.1.0 / カテゴリ: 3次元再構成 | ||||||||||||||||||||||||
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.16 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 272007 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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