+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7xog | ||||||||||||
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タイトル | Cryo-EM structure of S glycoprotein encoded by the Covid-19 mRNA vaccine candidate RQ3013 (Postfusion state) | ||||||||||||
要素 | Spike glycoprotein,peptide | ||||||||||||
キーワード | VIRAL PROTEIN / Spike / mRNA vaccine / SARS-CoV-2 / S clycoprotein | ||||||||||||
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 (SARS コロナウイルス) synthetic construct (人工物) | ||||||||||||
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: 3.5 Å | ||||||||||||
データ登録者 | Wu, Z. / Yu, Z. / Tan, S. / Lu, J. / Lu, G. / Lin, J. | ||||||||||||
資金援助 | 中国, 3件
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引用 | ジャーナル: Sci Bull (Beijing) / 年: 2023 タイトル: Preclinical evaluation of RQ3013, a broad-spectrum mRNA vaccine against SARS-CoV-2 variants. 著者: Shudan Tan / Jinghua Zhao / Xue Hu / Yufeng Li / Zihan Wu / Guoliang Lu / Zhaoli Yu / Binhe Du / Yan Liu / Li Li / Yuchen Chen / Ye Li / Yanfeng Yao / Xiaoyu Zhang / Juhong Rao / Ge Gao / Yun ...著者: Shudan Tan / Jinghua Zhao / Xue Hu / Yufeng Li / Zihan Wu / Guoliang Lu / Zhaoli Yu / Binhe Du / Yan Liu / Li Li / Yuchen Chen / Ye Li / Yanfeng Yao / Xiaoyu Zhang / Juhong Rao / Ge Gao / Yun Peng / Hang Liu / Zhiming Yuan / Jia Liu / Qianran Wang / Hengrui Hu / Xiaobo Gao / Hui Zhou / Hang Yu / Yingjie Xu / Wei Yu / Lin Feng / Manli Wang / Chao Shan / Jing Lu / Jinzhong Lin / 要旨: The global emergence of SARS-CoV-2 variants has led to increasing breakthrough infections in vaccinated populations, calling for an urgent need to develop more effective and broad-spectrum vaccines ...The global emergence of SARS-CoV-2 variants has led to increasing breakthrough infections in vaccinated populations, calling for an urgent need to develop more effective and broad-spectrum vaccines to combat COVID-19. Here we report the preclinical development of RQ3013, an mRNA vaccine candidate intended to bring broad protection against SARS-CoV-2 variants of concern (VOCs). RQ3013, which contains pseudouridine-modified mRNAs formulated in lipid nanoparticles, encodes the spike (S) protein harboring a combination of mutations responsible for immune evasion of VOCs. Here we characterized the expressed S immunogen and evaluated the immunogenicity, efficacy, and safety of RQ3013 in various animal models. RQ3013 elicited robust immune responses in mice, hamsters, and nonhuman primates (NHP). It can induce high titers of antibodies with broad cross-neutralizing ability against the wild-type, B.1.1.7, B.1.351, B.1.617.2, and the newly emerging Omicron variants. In mice and NHP, two doses of RQ3013 protected the upper and lower respiratory tract against infection by SARS-CoV-2 and its variants. Furthermore, our safety assessment of RQ3013 in NHP showed no observable adverse effects. These results provide strong support for the evaluation of RQ3013 in clinical trials and suggest that it may be a promising candidate for broad protection against COVID-19 and its variants. | ||||||||||||
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 | 7xog.cif.gz | 278.6 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7xog.ent.gz | 197.1 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7xog.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 | 7xog_validation.pdf.gz | 2.3 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7xog_full_validation.pdf.gz | 2.4 MB | 表示 | |
XML形式データ | 7xog_validation.xml.gz | 59.1 KB | 表示 | |
CIF形式データ | 7xog_validation.cif.gz | 81.7 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/xo/7xog ftp://data.pdbj.org/pub/pdb/validation_reports/xo/7xog | HTTPS FTP |
-関連構造データ
関連構造データ | 33347MC 7xoeC 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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1 |
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-要素
-タンパク質 , 1種, 3分子 CAB
#1: タンパク質 | 分子量: 142800.703 Da / 分子数: 3 / 由来タイプ: 組換発現 由来: (組換発現) Severe acute respiratory syndrome coronavirus (SARS コロナウイルス), (組換発現) synthetic construct (人工物) 遺伝子: S, 2 / プラスミド: pcDNA3.1 / 発現宿主: Homo sapiens (ヒト) / 株 (発現宿主): HEK293F / 参照: UniProt: P0DTC2 |
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-糖 , 5種, 27分子
#2: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #3: 多糖 | alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #4: 多糖 | #5: 糖 | ChemComp-NAG / #6: 糖 | |
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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 | 名称: Severe acute respiratory syndrome coronavirus / タイプ: COMPLEX 詳細: the full-length S glycoprotein encoded by the Covid-19 mRNA vaccine candidate RQ3013 Entity ID: #1 / 由来: RECOMBINANT |
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分子量 | 実験値: NO |
由来(天然) | 生物種: Severe acute respiratory syndrome coronavirus (SARS コロナウイルス) 株: chimera strain |
由来(組換発現) | 生物種: Homo sapiens (ヒト) / 株: HEK293F / 細胞: HEK293F / プラスミド: pcDNA3.1 |
緩衝液 | pH: 7.5 |
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: Talos Arctica / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TECNAI ARCTICA |
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 / 最大 デフォーカス(公称値): 5000 nm / 最小 デフォーカス(公称値): 1200 nm |
撮影 | 電子線照射量: 1.25 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
-解析
CTF補正 | タイプ: NONE |
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3次元再構成 | 解像度: 3.5 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 19454 / 対称性のタイプ: POINT |