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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: 7r8n | ||||||
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タイトル | Structure of the SARS-CoV-2 S 6P trimer in complex with neutralizing antibody C051 | ||||||
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![]() | VIRAL PROTEIN/IMMUNE SYSTEM / SARS-CoV-2 / receptor binding domain / RBD / neutralizing antibody / COVID-19 / spike / ANTIVIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex | ||||||
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 / 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 / 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: 3.55 Å | ||||||
![]() | Barnes, C.O. / Bjorkman, P.J. | ||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Affinity maturation of SARS-CoV-2 neutralizing antibodies confers potency, breadth, and resilience to viral escape mutations. 著者: Frauke Muecksch / Yiska Weisblum / Christopher O Barnes / Fabian Schmidt / Dennis Schaefer-Babajew / Zijun Wang / Julio C C Lorenzi / Andrew I Flyak / Andrew T DeLaitsch / Kathryn E Huey- ...著者: Frauke Muecksch / Yiska Weisblum / Christopher O Barnes / Fabian Schmidt / Dennis Schaefer-Babajew / Zijun Wang / Julio C C Lorenzi / Andrew I Flyak / Andrew T DeLaitsch / Kathryn E Huey-Tubman / Shurong Hou / Celia A Schiffer / Christian Gaebler / Justin Da Silva / Daniel Poston / Shlomo Finkin / Alice Cho / Melissa Cipolla / Thiago Y Oliveira / Katrina G Millard / Victor Ramos / Anna Gazumyan / Magdalena Rutkowska / Marina Caskey / Michel C Nussenzweig / Pamela J Bjorkman / Theodora Hatziioannou / Paul D Bieniasz / ![]() 要旨: Antibodies elicited by infection accumulate somatic mutations in germinal centers that can increase affinity for cognate antigens. We analyzed 6 independent groups of clonally related severe acute ...Antibodies elicited by infection accumulate somatic mutations in germinal centers that can increase affinity for cognate antigens. We analyzed 6 independent groups of clonally related severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) Spike receptor-binding domain (RBD)-specific antibodies from 5 individuals shortly after infection and later in convalescence to determine the impact of maturation over months. In addition to increased affinity and neutralization potency, antibody evolution changed the mutational pathways for the acquisition of viral resistance and restricted neutralization escape options. For some antibodies, maturation imposed a requirement for multiple substitutions to enable escape. For certain antibodies, affinity maturation enabled the neutralization of circulating SARS-CoV-2 variants of concern and heterologous sarbecoviruses. Antibody-antigen structures revealed that these properties resulted from substitutions that allowed additional variability at the interface with the RBD. These findings suggest that increasing antibody diversity through prolonged or repeated antigen exposure may improve protection against diversifying SARS-CoV-2 populations, and perhaps against other pandemic threat coronaviruses. #1: ジャーナル: bioRxiv / 年: 2021 タイトル: Development of potency, breadth and resilience to viral escape mutations in SARS-CoV-2 neutralizing antibodies. 著者: Frauke Muecksch / Yiska Weisblum / Christopher O Barnes / Fabian Schmidt / Dennis Schaefer-Babajew / Julio C C Lorenzi / Andrew I Flyak / Andrew T DeLaitsch / Kathryn E Huey-Tubman / Shurong ...著者: Frauke Muecksch / Yiska Weisblum / Christopher O Barnes / Fabian Schmidt / Dennis Schaefer-Babajew / Julio C C Lorenzi / Andrew I Flyak / Andrew T DeLaitsch / Kathryn E Huey-Tubman / Shurong Hou / Celia A Schiffer / Christian Gaebler / Zijun Wang / Justin Da Silva / Daniel Poston / Shlomo Finkin / Alice Cho / Melissa Cipolla / Thiago Y Oliveira / Katrina G Millard / Victor Ramos / Anna Gazumyan / Magdalena Rutkowska / Marina Caskey / Michel C Nussenzweig / Pamela J Bjorkman / Theodora Hatziioannou / Paul D Bieniasz / ![]() 要旨: Antibodies elicited in response to infection undergo somatic mutation in germinal centers that can result in higher affinity for the cognate antigen. To determine the effects of somatic mutation on ...Antibodies elicited in response to infection undergo somatic mutation in germinal centers that can result in higher affinity for the cognate antigen. To determine the effects of somatic mutation on the properties of SARS-CoV-2 spike receptor-binding domain (RBD)-specific antibodies, we analyzed six independent antibody lineages. As well as increased neutralization potency, antibody evolution changed pathways for acquisition of resistance and, in some cases, restricted the range of neutralization escape options. For some antibodies, maturation apparently imposed a requirement for multiple spike mutations to enable escape. For certain antibody lineages, maturation enabled neutralization of circulating SARS-CoV-2 variants of concern and heterologous sarbecoviruses. Antibody-antigen structures revealed that these properties resulted from substitutions that allowed additional variability at the interface with the RBD. These findings suggest that increasing antibody diversity through prolonged or repeated antigen exposure may improve protection against diversifying SARS-CoV-2 populations, and perhaps against other pandemic threat coronaviruses. | ||||||
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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PDBx/mmCIF形式 | ![]() | 677.6 KB | 表示 | ![]() |
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PDB形式 | ![]() | 556.1 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
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-検証レポート
文書・要旨 | ![]() | 1.3 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.3 MB | 表示 | |
XML形式データ | ![]() | 116.8 KB | 表示 | |
CIF形式データ | ![]() | 173.9 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 24319MC ![]() 7n3eC ![]() 7n3fC ![]() 7n3gC ![]() 7n3hC ![]() 7n3iC ![]() 7r8lC ![]() 7r8mC ![]() 7r8oC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 ( |
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類似構造データ |
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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: 141157.391 Da / 分子数: 3 / 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): HEK293 / 発現宿主: ![]() #2: 抗体 | 分子量: 25418.262 Da / 分子数: 3 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #3: 抗体 | 分子量: 22866.094 Da / 分子数: 3 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #4: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #5: 糖 | ChemComp-NAG / 研究の焦点であるリガンドがあるか | N | |
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-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: Ternary complex of SARS-CoV-2 S 6P trimer with C051 Fabs タイプ: COMPLEX / Entity ID: #1-#3 / 由来: RECOMBINANT | |||||||||||||||
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分子量 | 値: .72 MDa / 実験値: YES | |||||||||||||||
由来(天然) |
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由来(組換発現) | 生物種: ![]() | |||||||||||||||
緩衝液 | pH: 8 | |||||||||||||||
緩衝液成分 |
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試料 | 濃度: 3 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES / 詳細: Monodisperse sample | |||||||||||||||
試料支持 | 詳細: .2 mA / グリッドの材料: GOLD / グリッドのサイズ: 300 divisions/in. / 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 / 詳細: 3s blot, 0 blot force |
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電子顕微鏡撮影
実験機器 | ![]() モデル: Talos Arctica / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TALOS ARCTICA |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD / 倍率(補正後): 45000 X / 最小 デフォーカス(公称値): 700 nm / 最大 デフォーカス(補正後): 2000 nm / C2レンズ絞り径: 50 µm / アライメント法: COMA FREE |
試料ホルダ | 凍結剤: NITROGEN 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
撮影 | 平均露光時間: 3.6 sec. / 電子線照射量: 60 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 撮影したグリッド数: 1 / 実像数: 3402 |
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解析
ソフトウェア | 名称: PHENIX / バージョン: 1.19.1_4122: / 分類: 精密化 | ||||||||||||||||||||||||
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EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
粒子像の選択 | 選択した粒子像数: 390630 | ||||||||||||||||||||||||
対称性 | 点対称性: C3 (3回回転対称) | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.55 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 134506 / クラス平均像の数: 1 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
原子モデル構築 | B value: 64.5 / プロトコル: RIGID BODY FIT / 空間: REAL | ||||||||||||||||||||||||
原子モデル構築 | PDB-ID: 7K90 | ||||||||||||||||||||||||
拘束条件 |
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