+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-32718 | |||||||||
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タイトル | Local CryoEM structure of the SARS-CoV-2 S6P(B.1.1.529) in complex with BD55-3152 Fab | |||||||||
マップデータ | ||||||||||
試料 |
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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 / Attachment and Entry / membrane fusion / 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 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.5 Å | |||||||||
データ登録者 | Du S / Xiao JY | |||||||||
資金援助 | 1件
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引用 | ジャーナル: Nature / 年: 2022 タイトル: BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection. 著者: Yunlong Cao / Ayijiang Yisimayi / Fanchong Jian / Weiliang Song / Tianhe Xiao / Lei Wang / Shuo Du / Jing Wang / Qianqian Li / Xiaosu Chen / Yuanling Yu / Peng Wang / Zhiying Zhang / Pulan ...著者: Yunlong Cao / Ayijiang Yisimayi / Fanchong Jian / Weiliang Song / Tianhe Xiao / Lei Wang / Shuo Du / Jing Wang / Qianqian Li / Xiaosu Chen / Yuanling Yu / Peng Wang / Zhiying Zhang / Pulan Liu / Ran An / Xiaohua Hao / Yao Wang / Jing Wang / Rui Feng / Haiyan Sun / Lijuan Zhao / Wen Zhang / Dong Zhao / Jiang Zheng / Lingling Yu / Can Li / Na Zhang / Rui Wang / Xiao Niu / Sijie Yang / Xuetao Song / Yangyang Chai / Ye Hu / Yansong Shi / Linlin Zheng / Zhiqiang Li / Qingqing Gu / Fei Shao / Weijin Huang / Ronghua Jin / Zhongyang Shen / Youchun Wang / Xiangxi Wang / Junyu Xiao / Xiaoliang Sunney Xie / 要旨: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility than the BA.2 lineage. The receptor binding and immune- ...Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility than the BA.2 lineage. The receptor binding and immune-evasion capability of these recently emerged variants require immediate investigation. Here, coupled with structural comparisons of the spike proteins, we show that BA.2.12.1, BA.4 and BA.5 (BA.4 and BA.5 are hereafter referred collectively to as BA.4/BA.5) exhibit similar binding affinities to BA.2 for the angiotensin-converting enzyme 2 (ACE2) receptor. Of note, BA.2.12.1 and BA.4/BA.5 display increased evasion of neutralizing antibodies compared with BA.2 against plasma from triple-vaccinated individuals or from individuals who developed a BA.1 infection after vaccination. To delineate the underlying antibody-evasion mechanism, we determined the escape mutation profiles, epitope distribution and Omicron-neutralization efficiency of 1,640 neutralizing antibodies directed against the receptor-binding domain of the viral spike protein, including 614 antibodies isolated from people who had recovered from BA.1 infection. BA.1 infection after vaccination predominantly recalls humoral immune memory directed against ancestral (hereafter referred to as wild-type (WT)) SARS-CoV-2 spike protein. The resulting elicited antibodies could neutralize both WT SARS-CoV-2 and BA.1 and are enriched on epitopes on spike that do not bind ACE2. However, most of these cross-reactive neutralizing antibodies are evaded by spike mutants L452Q, L452R and F486V. BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1. Nevertheless, these neutralizing antibodies are largely evaded by BA.2 and BA.4/BA.5 owing to D405N and F486V mutations, and react weakly to pre-Omicron variants, exhibiting narrow neutralization breadths. The therapeutic neutralizing antibodies bebtelovimab and cilgavimab can effectively neutralize BA.2.12.1 and BA.4/BA.5, whereas the S371F, D405N and R408S mutations undermine most broadly sarbecovirus-neutralizing antibodies. Together, our results indicate that Omicron may evolve mutations to evade the humoral immunity elicited by BA.1 infection, suggesting that BA.1-derived vaccine boosters may not achieve broad-spectrum protection against new Omicron variants. | |||||||||
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 | emd_32718.map.gz | 168.2 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-32718-v30.xml emd-32718.xml | 13.5 KB 13.5 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_32718.png | 57.8 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-32718 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-32718 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_32718_validation.pdf.gz | 420.3 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_32718_full_validation.pdf.gz | 419.9 KB | 表示 | |
XML形式データ | emd_32718_validation.xml.gz | 6.8 KB | 表示 | |
CIF形式データ | emd_32718_validation.cif.gz | 7.8 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32718 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32718 | HTTPS FTP |
-関連構造データ
関連構造データ | 7wr8MC 7wrlC 7wroC 7wrzC 7x6aC 7xiwC 7xixC 7xiyC 7xizC 7xnqC 7xnrC 7xnsC 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 (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
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_32718.map.gz / 形式: CCP4 / 大きさ: 178 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 1.04 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
-試料の構成要素
-全体 : complex of BD55-3152 with S6P
全体 | 名称: complex of BD55-3152 with S6P |
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要素 |
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-超分子 #1: complex of BD55-3152 with S6P
超分子 | 名称: complex of BD55-3152 with S6P / タイプ: complex / キメラ: Yes / ID: 1 / 親要素: 0 / 含まれる分子: all |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
組換発現 | 生物種: Homo sapiens (ヒト) |
-分子 #1: Spike protein S1
分子 | 名称: Spike protein S1 / 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: Severe acute respiratory syndrome coronavirus 2 (ウイルス) |
分子量 | 理論値: 21.968818 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: NLCPFDEVFN ATRFASVYAW NRKRISNCVA DYSVLYNLAP FFTFKCYGVS PTKLNDLCFT NVYADSFVIR GDEVRQIAPG QTGNIADYN YKLPDDFTGC VIAWNSNKLD SKVSGNYNYL YRLFRKSNLK PFERDISTEI YQAGNKPCNG VAGFNCYFPL R SYSFRPTY ...文字列: NLCPFDEVFN ATRFASVYAW NRKRISNCVA DYSVLYNLAP FFTFKCYGVS PTKLNDLCFT NVYADSFVIR GDEVRQIAPG QTGNIADYN YKLPDDFTGC VIAWNSNKLD SKVSGNYNYL YRLFRKSNLK PFERDISTEI YQAGNKPCNG VAGFNCYFPL R SYSFRPTY GVGHQPYRVV VLSFELLHAP ATVCG |
-分子 #2: BD55-3152H
分子 | 名称: BD55-3152H / 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: Homo sapiens (ヒト) |
分子量 | 理論値: 27.819539 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MGWSLILLFL VAVATRVLSQ VQLVQSGAEV KKPGASVIVS CKASGYRFIS HYIHWVRQAP GQGLEWMGKI DPSGRGTTYA QKLQGRVSV TRDTSTSSVY MALSGLRSDD TAVYYCARDR FPLSDPYVWG SPLGGLDVWG QGTTVIVSSA STKGPSVFPL A PSSKSTSG ...文字列: MGWSLILLFL VAVATRVLSQ VQLVQSGAEV KKPGASVIVS CKASGYRFIS HYIHWVRQAP GQGLEWMGKI DPSGRGTTYA QKLQGRVSV TRDTSTSSVY MALSGLRSDD TAVYYCARDR FPLSDPYVWG SPLGGLDVWG QGTTVIVSSA STKGPSVFPL A PSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NT KVDKKVE PKSCDKTHHH HHH |
-分子 #3: BD55-3152L
分子 | 名称: BD55-3152L / 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: Homo sapiens (ヒト) |
分子量 | 理論値: 24.830543 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MGWSCIILFL VATATGVHSS YDLTQPPSVS VSPGQTARIT CSGDALPSQY VYWYQQRPGQ APVLVMYKDS ERPPGIPERF SGSTSGTTA TLTITGVQAE DEADYYCQSA DASTTYHVFG GGTKVTVVGQ PKAAPSVTLF PPSSEELQAN KATLVCLISD F YPGAVTVA ...文字列: MGWSCIILFL VATATGVHSS YDLTQPPSVS VSPGQTARIT CSGDALPSQY VYWYQQRPGQ APVLVMYKDS ERPPGIPERF SGSTSGTTA TLTITGVQAE DEADYYCQSA DASTTYHVFG GGTKVTVVGQ PKAAPSVTLF PPSSEELQAN KATLVCLISD F YPGAVTVA WKADSSPVKA GVETTTPSKQ SNNKYAASSY LSLTPEQWKS HRSYSCQVTH EGSTVEKTVA PTECS |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
緩衝液 | pH: 7.2 |
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凍結 | 凍結剤: ETHANE |
-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 K2 QUANTUM (4k 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: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: DARK FIELD / 最大 デフォーカス(公称値): 1.5 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 |
-画像解析
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.5 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 282833 |
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初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |