+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7n9b | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
タイトル | Potent neutralizing nanobodies resist convergent circulating variants of SARS-CoV-2 by targeting novel and conserved epitopes-CovS with NB21 | ||||||||||||
要素 |
| ||||||||||||
キーワード | VIRAL PROTEIN/IMMUNE SYSTEM / CovS NB21 nanobody / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex | ||||||||||||
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 / membrane fusion / receptor-mediated endocytosis of virus by host cell / 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) Lama glama (ラマ) | ||||||||||||
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: 3.8 Å | ||||||||||||
データ登録者 | Sun, D. / Zhang, C. / Shi, Y. | ||||||||||||
資金援助 | 米国, 3件
| ||||||||||||
引用 | ジャーナル: bioRxiv / 年: 2021 タイトル: Potent neutralizing nanobodies resist convergent circulating variants of SARS-CoV-2 by targeting novel and conserved epitopes. 著者: Dapeng Sun / Zhe Sang / Yong Joon Kim / Yufei Xiang / Tomer Cohen / Anna K Belford / Alexis Huet / James F Conway / Ji Sun / Derek J Taylor / Dina Schneidman-Duhovny / Cheng Zhang / Wei Huang / Yi Shi / 要旨: There is an urgent need to develop effective interventions resistant to the evolving variants of SARS-CoV-2. Nanobodies (Nbs) are stable and cost-effective agents that can be delivered by novel ...There is an urgent need to develop effective interventions resistant to the evolving variants of SARS-CoV-2. Nanobodies (Nbs) are stable and cost-effective agents that can be delivered by novel aerosolization route to treat SARS-CoV-2 infections efficiently. However, it remains unknown if they possess broadly neutralizing activities against the prevalent circulating strains. We found that potent neutralizing Nbs are highly resistant to the convergent variants of concern that evade a large panel of neutralizing antibodies (Abs) and significantly reduce the activities of convalescent or vaccine-elicited sera. Subsequent determination of 9 high-resolution structures involving 6 potent neutralizing Nbs by cryoelectron microscopy reveals conserved and novel epitopes on virus spike inaccessible to Abs. Systematic structural comparison of neutralizing Abs and Nbs provides critical insights into how Nbs uniquely target the spike to achieve high-affinity and broadly neutralizing activity against the evolving virus. Our study will inform the rational design of novel pan-coronavirus vaccines and therapeutics. | ||||||||||||
履歴 |
|
-構造の表示
ムービー |
ムービービューア |
---|---|
構造ビューア | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7n9b.cif.gz | 568.3 KB | 表示 | PDBx/mmCIF形式 |
---|---|---|---|---|
PDB形式 | pdb7n9b.ent.gz | 450.4 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7n9b.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 | 7n9b_validation.pdf.gz | 1 MB | 表示 | wwPDB検証レポート |
---|---|---|---|---|
文書・詳細版 | 7n9b_full_validation.pdf.gz | 1.1 MB | 表示 | |
XML形式データ | 7n9b_validation.xml.gz | 87.9 KB | 表示 | |
CIF形式データ | 7n9b_validation.cif.gz | 134.3 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/n9/7n9b ftp://data.pdbj.org/pub/pdb/validation_reports/n9/7n9b | HTTPS FTP |
-関連構造データ
-リンク
-集合体
登録構造単位 |
|
---|---|
1 |
|
-要素
#1: タンパク質 | 分子量: 152312.750 Da / 分子数: 3 / 由来タイプ: 組換発現 詳細: Pre-fusion stabilized HexaPro construct, including six proline substitutions and furin cleavage site RRAR 682-685 mutated to GSAS 由来: (組換発現) Severe acute respiratory syndrome coronavirus 2 (ウイルス) 遺伝子: S, 2 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P0DTC2 #2: 抗体 | 分子量: 15770.573 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Lama glama (ラマ) / 発現宿主: Escherichia coli (大腸菌) / 株 (発現宿主): BL21(DE3) Has protein modification | Y | |
---|
-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
---|---|
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 |
| ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
分子量 | 実験値: NO | ||||||||||||||||||||||||
由来(天然) |
| ||||||||||||||||||||||||
由来(組換発現) |
| ||||||||||||||||||||||||
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: Titan Krios / 画像提供: FEI Company |
---|---|
顕微鏡 | モデル: FEI TITAN KRIOS |
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 |
撮影 | 電子線照射量: 60 e/Å2 / 検出モード: COUNTING フィルム・検出器のモデル: FEI FALCON III (4k x 4k) |
-解析
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
---|---|
3次元再構成 | 解像度: 3.8 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 91000 / 対称性のタイプ: POINT |