+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7my2 | ||||||
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タイトル | CryoEM structure of neutralizing nanobody Nb30 in complex with SARS-CoV2 spike | ||||||
要素 |
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キーワード | IMMUNE SYSTEM/VIRAL PROTEIN / SARS-CoV2 / nanobody / neutralizing / spike / IMMUNE SYSTEM-VIRAL PROTEIN 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 / 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 / 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) Mus musculus (ハツカネズミ) | ||||||
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: 2.65 Å | ||||||
データ登録者 | Xu, K. / Kwong, P.D. | ||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: Nature / 年: 2021 タイトル: Nanobodies from camelid mice and llamas neutralize SARS-CoV-2 variants. 著者: Jianliang Xu / Kai Xu / Seolkyoung Jung / Andrea Conte / Jenna Lieberman / Frauke Muecksch / Julio Cesar Cetrulo Lorenzi / Solji Park / Fabian Schmidt / Zijun Wang / Yaoxing Huang / Yang Luo ...著者: Jianliang Xu / Kai Xu / Seolkyoung Jung / Andrea Conte / Jenna Lieberman / Frauke Muecksch / Julio Cesar Cetrulo Lorenzi / Solji Park / Fabian Schmidt / Zijun Wang / Yaoxing Huang / Yang Luo / Manoj S Nair / Pengfei Wang / Jonathan E Schulz / Lino Tessarollo / Tatsiana Bylund / Gwo-Yu Chuang / Adam S Olia / Tyler Stephens / I-Ting Teng / Yaroslav Tsybovsky / Tongqing Zhou / Vincent Munster / David D Ho / Theodora Hatziioannou / Paul D Bieniasz / Michel C Nussenzweig / Peter D Kwong / Rafael Casellas / 要旨: Since the start of the COVID-19 pandemic, SARS-CoV-2 has caused millions of deaths worldwide. Although a number of vaccines have been deployed, the continual evolution of the receptor-binding domain ...Since the start of the COVID-19 pandemic, SARS-CoV-2 has caused millions of deaths worldwide. Although a number of vaccines have been deployed, the continual evolution of the receptor-binding domain (RBD) of the virus has challenged their efficacy. In particular, the emerging variants B.1.1.7, B.1.351 and P.1 (first detected in the UK, South Africa and Brazil, respectively) have compromised the efficacy of sera from patients who have recovered from COVID-19 and immunotherapies that have received emergency use authorization. One potential alternative to avert viral escape is the use of camelid VHHs (variable heavy chain domains of heavy chain antibody (also known as nanobodies)), which can recognize epitopes that are often inaccessible to conventional antibodies. Here, we isolate anti-RBD nanobodies from llamas and from mice that we engineered to produce VHHs cloned from alpacas, dromedaries and Bactrian camels. We identified two groups of highly neutralizing nanobodies. Group 1 circumvents antigenic drift by recognizing an RBD region that is highly conserved in coronaviruses but rarely targeted by human antibodies. Group 2 is almost exclusively focused to the RBD-ACE2 interface and does not neutralize SARS-CoV-2 variants that carry E484K or N501Y substitutions. However, nanobodies in group 2 retain full neutralization activity against these variants when expressed as homotrimers, and-to our knowledge-rival the most potent antibodies against SARS-CoV-2 that have been produced to date. These findings suggest that multivalent nanobodies overcome SARS-CoV-2 mutations through two separate mechanisms: enhanced avidity for the ACE2-binding domain and recognition of conserved epitopes that are largely inaccessible to human antibodies. Therefore, although new SARS-CoV-2 mutants will continue to emerge, nanobodies represent promising tools to prevent COVID-19 mortality when vaccines are compromised. | ||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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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 | 7my2.cif.gz | 622.8 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7my2.ent.gz | 522.1 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7my2.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 | 7my2_validation.pdf.gz | 1.2 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7my2_full_validation.pdf.gz | 1.2 MB | 表示 | |
XML形式データ | 7my2_validation.xml.gz | 83 KB | 表示 | |
CIF形式データ | 7my2_validation.cif.gz | 134.8 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/my/7my2 ftp://data.pdbj.org/pub/pdb/validation_reports/my/7my2 | HTTPS FTP |
-関連構造データ
-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 / 抗体 , 2種, 6分子 BCEHAD
#1: タンパク質 | 分子量: 142427.438 Da / 分子数: 3 変異: R682G, R683S, R685S, F817P, A892P, A899P, A942P, K986P, V987P 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 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P0DTC2 #2: 抗体 | 分子量: 14210.731 Da / 分子数: 3 / 由来タイプ: 組換発現 / 由来: (組換発現) Mus musculus (ハツカネズミ) / 発現宿主: Escherichia coli (大腸菌) |
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-糖 , 4種, 45分子
#3: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #4: 多糖 | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #5: 多糖 | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | #6: 糖 | ChemComp-NAG / |
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-詳細
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 |
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分子量 |
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由来(天然) |
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由来(組換発現) |
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緩衝液 | pH: 7.4 / 詳細: 5mM Hepes pH7.4, 150mM NaCl | ||||||||||||||||||||||||||||
緩衝液成分 | 式: HBS | ||||||||||||||||||||||||||||
試料 | 濃度: 0.5 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | ||||||||||||||||||||||||||||
試料支持 | グリッドの材料: GOLD / グリッドのサイズ: 400 divisions/in. / グリッドのタイプ: Quantifoil R2/2 | ||||||||||||||||||||||||||||
急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 95 % / 凍結前の試料温度: 293 K |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
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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 / C2レンズ絞り径: 70 µm |
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: 2 sec. / 電子線照射量: 40.3 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: 6796 |
-解析
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: 1666677 | ||||||||||||||||||||||||||||||||||||
対称性 | 点対称性: C1 (非対称) | ||||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 2.65 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 333232 / クラス平均像の数: 48 / 対称性のタイプ: POINT | ||||||||||||||||||||||||||||||||||||
原子モデル構築 | プロトコル: FLEXIBLE FIT / 空間: REAL | ||||||||||||||||||||||||||||||||||||
原子モデル構築 | PDB-ID: 6XKL PDB chain-ID: A |