+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8vao | ||||||
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タイトル | Simulation-driven design of prefusion stabilized SARS-CoV-2 spike S2 antigen | ||||||
要素 | Spike protein S2 | ||||||
キーワード | VIRAL PROTEIN / SARS-CoV-2 / spike protein / viral fusion / viral glycoprotein | ||||||
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 | 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: 2.8 Å | ||||||
データ登録者 | Zhou, L. / McLellan, J.S. | ||||||
資金援助 | 1件
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引用 | ジャーナル: Nat Commun / 年: 2024 タイトル: Simulation-driven design of stabilized SARS-CoV-2 spike S2 immunogens. 著者: Xandra Nuqui / Lorenzo Casalino / Ling Zhou / Mohamed Shehata / Albert Wang / Alexandra L Tse / Anupam A Ojha / Fiona L Kearns / Mia A Rosenfeld / Emily Happy Miller / Cory M Acreman / Surl- ...著者: Xandra Nuqui / Lorenzo Casalino / Ling Zhou / Mohamed Shehata / Albert Wang / Alexandra L Tse / Anupam A Ojha / Fiona L Kearns / Mia A Rosenfeld / Emily Happy Miller / Cory M Acreman / Surl-Hee Ahn / Kartik Chandran / Jason S McLellan / Rommie E Amaro / 要旨: The full-length prefusion-stabilized SARS-CoV-2 spike (S) is the principal antigen of COVID-19 vaccines. Vaccine efficacy has been impacted by emerging variants of concern that accumulate most of the ...The full-length prefusion-stabilized SARS-CoV-2 spike (S) is the principal antigen of COVID-19 vaccines. Vaccine efficacy has been impacted by emerging variants of concern that accumulate most of the sequence modifications in the immunodominant S1 subunit. S2, in contrast, is the most evolutionarily conserved region of the spike and can elicit broadly neutralizing and protective antibodies. Yet, S2's usage as an alternative vaccine strategy is hampered by its general instability. Here, we use a simulation-driven approach to design S2-only immunogens stabilized in a closed prefusion conformation. Molecular simulations provide a mechanistic characterization of the S2 trimer's opening, informing the design of tryptophan substitutions that impart kinetic and thermodynamic stabilization. Structural characterization via cryo-EM shows the molecular basis of S2 stabilization in the closed prefusion conformation. Informed by molecular simulations and corroborated by experiments, we report an engineered S2 immunogen that exhibits increased protein expression, superior thermostability, and preserved immunogenicity against sarbecoviruses. | ||||||
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 | 8vao.cif.gz | 475.9 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8vao.ent.gz | 398.3 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8vao.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 | 8vao_validation.pdf.gz | 1.1 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 8vao_full_validation.pdf.gz | 1.1 MB | 表示 | |
XML形式データ | 8vao_validation.xml.gz | 52.8 KB | 表示 | |
CIF形式データ | 8vao_validation.cif.gz | 77.4 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/va/8vao ftp://data.pdbj.org/pub/pdb/validation_reports/va/8vao | HTTPS FTP |
-関連構造データ
関連構造データ | 43097MC 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 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
-集合体
登録構造単位 |
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-要素
#1: タンパク質 | 分子量: 56323.484 Da / 分子数: 3 変異: S704C, K790C, F817P, A892P, A899P, A942P, Q957E, K986P, V987P, V991W, T998W 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 / 細胞株 (発現宿主): Freestyle 293F / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P0DTC2 #2: 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 |
-試料調製
構成要素 | 名称: SARS-CoV-2 spike S2 trimer / タイプ: COMPLEX / Entity ID: #1 / 由来: RECOMBINANT |
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由来(天然) | 生物種: Severe acute respiratory syndrome coronavirus 2 (ウイルス) |
由来(組換発現) | 生物種: Homo sapiens (ヒト) / 細胞: Freestyle 293F |
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
顕微鏡 | モデル: TFS GLACIOS |
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電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 200 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD / 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: 50 e/Å2 フィルム・検出器のモデル: FEI FALCON IV (4k x 4k) |
-解析
EMソフトウェア | 名称: PHENIX / バージョン: 1.20.1_4487: / カテゴリ: モデル精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: NONE | ||||||||||||||||||||||||
3次元再構成 | 解像度: 2.8 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 249447 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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