+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8ywx | ||||||
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タイトル | the complex structure of the H4B6 Fab with the RBD of Omicron BA.5 S protein | ||||||
要素 |
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キーワード | VIRAL PROTEIN/IMMUNE SYSTEM / antibody / 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 / 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 | Homo sapiens (ヒト) 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: 3.4 Å | ||||||
データ登録者 | Xia, L.Y. / Zhang, Y.Y. / Zhou, Q. | ||||||
資金援助 | 1件
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引用 | ジャーナル: Emerg Microbes Infect / 年: 2024 タイトル: A novel bispecific antibody targeting two overlapping epitopes in RBD improves neutralizing potency and breadth against SARS-CoV-2. 著者: Hancong Sun / Lingyun Xia / Jianhua Li / Yuanyuan Zhang / Guanying Zhang / Ping Huang / Xingxing Wang / Yue Cui / Ting Fang / Pengfei Fan / Qiang Zhou / Xiangyang Chi / Changming Yu / 要旨: SARS-CoV-2 has been evolving into a large number of variants, including the highly pathogenic Delta variant, and the currently prevalent Omicron subvariants with extensive evasion capability, which ...SARS-CoV-2 has been evolving into a large number of variants, including the highly pathogenic Delta variant, and the currently prevalent Omicron subvariants with extensive evasion capability, which raises an urgent need to develop new broad-spectrum neutralizing antibodies. Herein, we engineer two IgG-(scFv) form bispecific antibodies with overlapping epitopes (bsAb1) or non-overlapping epitopes (bsAb2). Both bsAbs are significantly superior to the parental monoclonal antibodies in terms of their antigen-binding and virus-neutralizing activities against all tested circulating SARS-CoV-2 variants including currently dominant JN.1. The bsAb1 can efficiently neutralize all variants insensitive to parental monoclonal antibodies or the cocktail with IC lower than 20 ng/mL, even slightly better than bsAb2. Furthermore, the cryo-EM structures of bsAb1 in complex with the Omicron spike protein revealed that bsAb1 with overlapping epitopes effectively locked the S protein, which accounts for its conserved neutralization against Omicron variants. The bispecific antibody strategy engineered from overlapping epitopes provides a novel solution for dealing with viral immune evasion. | ||||||
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 | 8ywx.cif.gz | 153.4 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8ywx.ent.gz | 99.8 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8ywx.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 | 8ywx_validation.pdf.gz | 1.1 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 8ywx_full_validation.pdf.gz | 1.1 MB | 表示 | |
XML形式データ | 8ywx_validation.xml.gz | 36.2 KB | 表示 | |
CIF形式データ | 8ywx_validation.cif.gz | 50.5 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/yw/8ywx ftp://data.pdbj.org/pub/pdb/validation_reports/yw/8ywx | HTTPS FTP |
-関連構造データ
関連構造データ | 39646MC 8ywwC 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
#1: 抗体 | 分子量: 76157.969 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 発現宿主: Homo sapiens (ヒト) |
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#2: 抗体 | 分子量: 23574.154 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 発現宿主: Homo sapiens (ヒト) |
#3: タンパク質 | 分子量: 124212.977 Da / 分子数: 1 / 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) 株: Omicron/BA.5 / 遺伝子: S, 2 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P0DTC2 |
-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: the complex structure of the H4B6 Fab with the RBD of Omicron BA.5 S protein タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT | ||||||||||||
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由来(天然) |
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由来(組換発現) | 生物種: Homo sapiens (ヒト) | ||||||||||||
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 |
-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 / 最大 デフォーカス(公称値): 2200 nm / 最小 デフォーカス(公称値): 1200 nm |
撮影 | 電子線照射量: 50 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
-解析
EMソフトウェア | 名称: cryoSPARC / バージョン: v4 / カテゴリ: 3次元再構成 |
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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: 368678 / 対称性のタイプ: POINT |