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- EMDB-36789: Neutralization antibody ZCP3B4 bound with SARS-CoV-2 Omicron BA.5 RBD -
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基本情報
登録情報 | ![]() | |||||||||
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タイトル | Neutralization antibody ZCP3B4 bound with SARS-CoV-2 Omicron BA.5 RBD | |||||||||
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![]() | VIRAL PROTEIN | |||||||||
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 / symbiont-mediated-mediated suppression 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 / symbiont-mediated-mediated suppression of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell / membrane fusion / Attachment and Entry / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / host cell surface receptor binding / symbiont-mediated suppression of host innate immune response / receptor ligand activity / endocytosis involved in viral entry into host cell / 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 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.88 Å | |||||||||
![]() | Tang B / Dang S | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Ultrapotent class I neutralizing antibodies post Omicron breakthrough infection overcome broad SARS-CoV-2 escape variants. 著者: Mengxiao Luo / Runhong Zhou / Bingjie Tang / Hang Liu / Bohao Chen / Na Liu / Yufei Mo / Pengfei Zhang / Ye Lim Lee / Jonathan Daniel Ip / Allen Wing-Ho Chu / Wan-Mui Chan / Hiu-On Man / ...著者: Mengxiao Luo / Runhong Zhou / Bingjie Tang / Hang Liu / Bohao Chen / Na Liu / Yufei Mo / Pengfei Zhang / Ye Lim Lee / Jonathan Daniel Ip / Allen Wing-Ho Chu / Wan-Mui Chan / Hiu-On Man / Yuting Chen / Kelvin Kai-Wang To / Kwok-Yung Yuen / Shangyu Dang / Zhiwei Chen / ![]() 要旨: BACKGROUND: The spread of emerging SARS-CoV-2 immune escape sublineages, especially JN.1 and KP.2, has resulted in new waves of COVID-19 globally. The evolving memory B cell responses elicited by the ...BACKGROUND: The spread of emerging SARS-CoV-2 immune escape sublineages, especially JN.1 and KP.2, has resulted in new waves of COVID-19 globally. The evolving memory B cell responses elicited by the parental Omicron variants to subvariants with substantial antigenic drift remain incompletely investigated. 手法: Using the single B cell antibody cloning technology, we isolated single memory B cells, delineated the B cell receptor repertoire and conducted the pseudovirus-based assay for recovered ...手法: Using the single B cell antibody cloning technology, we isolated single memory B cells, delineated the B cell receptor repertoire and conducted the pseudovirus-based assay for recovered neutralizing antibodies (NAb) screening. We analyzed the cryo-EM structures of top broadly NAbs (bnAbs) and evaluated their in vivo efficacy (golden Syrian hamster model). FINDINGS: By investigating the evolution of human B cell immunity, we discovered a new panel of bnAbs arising from vaccinees after Omicron BA.2/BA.5 breakthrough infections. Two lead bnAbs ...FINDINGS: By investigating the evolution of human B cell immunity, we discovered a new panel of bnAbs arising from vaccinees after Omicron BA.2/BA.5 breakthrough infections. Two lead bnAbs neutralized major Omicron subvariants including JN.1 and KP.2 with IC values less than 10 ng/mL, representing ultrapotent receptor binding domain (RBD)-specific class I bnAbs. They belonged to the IGHV3-53/3-66 clonotypes instead of evolving from the pre-existing vaccine-induced IGHV1-58/IGKV3-20 bnAb ZCB11. Despite sequence diversity, they targeted previously unrecognized, highly conserved conformational epitopes in the receptor binding motif (RBM) for ultrapotent ACE2 blockade. The lead bnAb ZCP3B4 not only protected the lungs of hamsters intranasally challenged with BA.5.2, BQ.1.1 and XBB.1.5 but also prevented their contact transmission. INTERPRETATION: Our findings demonstrated that class I bnAbs have evolved an ultrapotent mode of action protecting against highly transmissible and broad Omicron escape variants, and their epitopes ...INTERPRETATION: Our findings demonstrated that class I bnAbs have evolved an ultrapotent mode of action protecting against highly transmissible and broad Omicron escape variants, and their epitopes are potential targets for novel bnAbs and vaccine development. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section. | |||||||||
履歴 |
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構造の表示
添付画像 |
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ダウンロードとリンク
-EMDBアーカイブ
マップデータ | ![]() | 62.6 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 22.3 KB 22.3 KB | 表示 表示 | ![]() |
画像 | ![]() | 112 KB | ||
Filedesc metadata | ![]() | 6.3 KB | ||
その他 | ![]() ![]() ![]() | 105 MB 115.8 MB 115.8 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 1.1 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.1 MB | 表示 | |
XML形式データ | ![]() | 13.9 KB | 表示 | |
CIF形式データ | ![]() | 16.4 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 8k19MC M: このマップから作成された原子モデル C: 同じ文献を引用 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||||||||||||||||||
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投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.06 Å | ||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-追加マップ: #1
ファイル | emd_36789_additional_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_36789_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #2
ファイル | emd_36789_half_map_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
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試料の構成要素
-全体 : Neutralization antibody ZCP3B4 bound with SARS-CoV-2 Omicron BA.5 RBD
全体 | 名称: Neutralization antibody ZCP3B4 bound with SARS-CoV-2 Omicron BA.5 RBD |
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要素 |
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-超分子 #1: Neutralization antibody ZCP3B4 bound with SARS-CoV-2 Omicron BA.5 RBD
超分子 | 名称: Neutralization antibody ZCP3B4 bound with SARS-CoV-2 Omicron BA.5 RBD タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all |
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由来(天然) | 生物種: ![]() ![]() |
-分子 #1: ZCP3B4 heavy chain
分子 | 名称: ZCP3B4 heavy chain / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 12.947513 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: EVQLVESGGG LVQPGGSLRL SCAASEIIVS SNYMRWVRQA PGKGLEWVSD IYPGGTTYYA DSVKGRFSIS RDNSKNTMYL QMSDLRAED TAVYYCARPI MGGRHGMDVW GQGTTVTVSS |
-分子 #2: ZCP3B4 light chain
分子 | 名称: ZCP3B4 light chain / タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 11.62799 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: DIQMTQSPAS LSASVGDRVT ISCQASQDIN KYLNWYQHKP GRAPKLLIFD ASTLETGVPS RFSGSGSGTH FTLTISSLQP EDIATYYCL QHDHVPLTFG GGTKVEIK |
-分子 #3: Spike protein S1
分子 | 名称: Spike protein S1 / タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 21.772561 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: NLCPFDEVFN ATKFPSVYAW ERKKISNCVA DYSVLYNFTP FSAFKCYGVS ATKLNDLCFS NVYADSFVVK GNDVSQIAPG QTGNIADYN YKLPDDFMGC VLAWNTRKID ATSTGNYNYR YRLFRKSNLK PFERDISTEI YQAGNKPCNG VAGVNCYFPL Q SYSFRPTY ...文字列: NLCPFDEVFN ATKFPSVYAW ERKKISNCVA DYSVLYNFTP FSAFKCYGVS ATKLNDLCFS NVYADSFVVK GNDVSQIAPG QTGNIADYN YKLPDDFMGC VLAWNTRKID ATSTGNYNYR YRLFRKSNLK PFERDISTEI YQAGNKPCNG VAGVNCYFPL Q SYSFRPTY GVGHQPYRVV VLSFELLHAP ATVCG UniProtKB: Spike glycoprotein |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
緩衝液 | pH: 7.5 |
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凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 平均電子線量: 50.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 照射モード: SPOT SCAN / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2.5 µm / 最小 デフォーカス(公称値): 1.0 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |