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基本情報
登録情報 | データベース: PDB / ID: 7q1z | |||||||||
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タイトル | Structure of formaldehyde cross-linked SARS-CoV-2 S glycoprotein | |||||||||
![]() | Spike glycoprotein | |||||||||
![]() | VIRAL PROTEIN / SARS-CoV-2 / glycoprotein / immunization | |||||||||
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 / Attachment and Entry / membrane fusion / symbiont-mediated suppression of host innate immune response / 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: 3.4 Å | |||||||||
![]() | Sulbaran, G. / Effantin, G. / Schoehn, G. / Weissenhorn, W. | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Immunization with synthetic SARS-CoV-2 S glycoprotein virus-like particles protects macaques from infection. 著者: Guidenn Sulbaran / Pauline Maisonnasse / Axelle Amen / Gregory Effantin / Delphine Guilligay / Nathalie Dereuddre-Bosquet / Judith A Burger / Meliawati Poniman / Marloes Grobben / Marlyse ...著者: Guidenn Sulbaran / Pauline Maisonnasse / Axelle Amen / Gregory Effantin / Delphine Guilligay / Nathalie Dereuddre-Bosquet / Judith A Burger / Meliawati Poniman / Marloes Grobben / Marlyse Buisson / Sebastian Dergan Dylon / Thibaut Naninck / Julien Lemaître / Wesley Gros / Anne-Sophie Gallouët / Romain Marlin / Camille Bouillier / Vanessa Contreras / Francis Relouzat / Daphna Fenel / Michel Thepaut / Isabelle Bally / Nicole Thielens / Franck Fieschi / Guy Schoehn / Sylvie van der Werf / Marit J van Gils / Rogier W Sanders / Pascal Poignard / Roger Le Grand / Winfried Weissenhorn / ![]() ![]() ![]() 要旨: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused an ongoing global health crisis. Here, we present as a vaccine candidate synthetic SARS-CoV-2 spike (S) ...The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused an ongoing global health crisis. Here, we present as a vaccine candidate synthetic SARS-CoV-2 spike (S) glycoprotein-coated lipid vesicles that resemble virus-like particles. Soluble S glycoprotein trimer stabilization by formaldehyde cross-linking introduces two major inter-protomer cross-links that keep all receptor-binding domains in the "down" conformation. Immunization of cynomolgus macaques with S coated onto lipid vesicles (S-LVs) induces high antibody titers with potent neutralizing activity against the vaccine strain, Alpha, Beta, and Gamma variants as well as T helper (Th)1 CD4-biased T cell responses. Although anti-receptor-binding domain (RBD)-specific antibody responses are initially predominant, the third immunization boosts significant non-RBD antibody titers. Challenging vaccinated animals with SARS-CoV-2 shows a complete protection through sterilizing immunity, which correlates with the presence of nasopharyngeal anti-S immunoglobulin G (IgG) and IgA titers. Thus, the S-LV approach is an efficient and safe vaccine candidate based on a proven classical approach for further development and clinical testing. #1: ![]() タイトル: Immunization with synthetic SARS-CoV-2 S glycoprotein virus-like particles protects macaques from infection. 著者: Guidenn Sulbaran / Pauline Maisonnasse / Axelle Amen / Gregory Effantin / Delphine Guilligay / Nathalie Dereuddre-Bosquet / Judith A Burger / Meliawati Poniman / Marloes Grobben / Marlyse ...著者: Guidenn Sulbaran / Pauline Maisonnasse / Axelle Amen / Gregory Effantin / Delphine Guilligay / Nathalie Dereuddre-Bosquet / Judith A Burger / Meliawati Poniman / Marloes Grobben / Marlyse Buisson / Sebastian Dergan Dylon / Thibaut Naninck / Julien Lemaître / Wesley Gros / Anne-Sophie Gallouët / Romain Marlin / Camille Bouillier / Vanessa Contreras / Francis Relouzat / Daphna Fenel / Michel Thepaut / Isabelle Bally / Nicole Thielens / Franck Fieschi / Guy Schoehn / Sylvie van der Werf / Marit J van Gils / Rogier W Sanders / Pascal Poignard / Roger Le Grand / Winfried Weissenhorn / ![]() ![]() ![]() 要旨: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused an ongoing global health crisis. Here, we present as a vaccine candidate synthetic SARS-CoV-2 spike (S) ...The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused an ongoing global health crisis. Here, we present as a vaccine candidate synthetic SARS-CoV-2 spike (S) glycoprotein-coated lipid vesicles that resemble virus-like particles. Soluble S glycoprotein trimer stabilization by formaldehyde cross-linking introduces two major inter-protomer cross-links that keep all receptor-binding domains in the "down" conformation. Immunization of cynomolgus macaques with S coated onto lipid vesicles (S-LVs) induces high antibody titers with potent neutralizing activity against the vaccine strain, Alpha, Beta, and Gamma variants as well as T helper (Th)1 CD4-biased T cell responses. Although anti-receptor-binding domain (RBD)-specific antibody responses are initially predominant, the third immunization boosts significant non-RBD antibody titers. Challenging vaccinated animals with SARS-CoV-2 shows a complete protection through sterilizing immunity, which correlates with the presence of nasopharyngeal anti-S immunoglobulin G (IgG) and IgA titers. Thus, the S-LV approach is an efficient and safe vaccine candidate based on a proven classical approach for further development and clinical testing. #2: ![]() タイトル: Immunization with synthetic SARS-CoV-2 S glycoprotein virus-like particles protects macaques from infection. 著者: Sulbaran, G. / Effantin, G. / Schoehn, G. / Weissenhorn, W. | |||||||||
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 | ![]() | 532.5 KB | 表示 | ![]() |
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PDB形式 | ![]() | 445.7 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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-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: 142399.375 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 / 発現宿主: ![]() #2: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #3: 糖 | ChemComp-NAG / 研究の焦点であるリガンドがあるか | Y | |
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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: Trimer of the SARS_CoV-2 S glycoprotein / タイプ: COMPLEX / Entity ID: #1 / 由来: RECOMBINANT |
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分子量 | 実験値: NO |
由来(天然) | 生物種: ![]() ![]() |
由来(組換発現) | 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
顕微鏡 | モデル: TFS GLACIOS |
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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: 40 e/Å2 / 検出モード: COUNTING フィルム・検出器のモデル: GATAN K2 SUMMIT (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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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
3次元再構成 | 解像度: 3.4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 126719 / 対称性のタイプ: POINT |