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データを開く
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基本情報
登録情報 | データベース: EMDB / ID: EMD-30635 | |||||||||
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タイトル | S-3C1-F3b structure, all the three RBDs are in the up conformation and each of them associates with a 3C1 Fab | |||||||||
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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 / 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 / symbiont-mediated suppression of host innate immune response / 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 | ![]() ![]() ![]() ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 4.3 Å | |||||||||
![]() | Cong Y / Liu CX | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Development and structural basis of a two-MAb cocktail for treating SARS-CoV-2 infections. 著者: Chao Zhang / Yifan Wang / Yuanfei Zhu / Caixuan Liu / Chenjian Gu / Shiqi Xu / Yalei Wang / Yu Zhou / Yanxing Wang / Wenyu Han / Xiaoyu Hong / Yong Yang / Xueyang Zhang / Tingfeng Wang / Cong ...著者: Chao Zhang / Yifan Wang / Yuanfei Zhu / Caixuan Liu / Chenjian Gu / Shiqi Xu / Yalei Wang / Yu Zhou / Yanxing Wang / Wenyu Han / Xiaoyu Hong / Yong Yang / Xueyang Zhang / Tingfeng Wang / Cong Xu / Qin Hong / Shutian Wang / Qiaoyu Zhao / Weihua Qiao / Jinkai Zang / Liangliang Kong / Fangfang Wang / Haikun Wang / Di Qu / Dimitri Lavillette / Hong Tang / Qiang Deng / Youhua Xie / Yao Cong / Zhong Huang / ![]() 要旨: The ongoing pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neutralizing antibodies against SARS-CoV-2 are an option for ...The ongoing pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neutralizing antibodies against SARS-CoV-2 are an option for drug development for treating COVID-19. Here, we report the identification and characterization of two groups of mouse neutralizing monoclonal antibodies (MAbs) targeting the receptor-binding domain (RBD) on the SARS-CoV-2 spike (S) protein. MAbs 2H2 and 3C1, representing the two antibody groups, respectively, bind distinct epitopes and are compatible in formulating a noncompeting antibody cocktail. A humanized version of the 2H2/3C1 cocktail is found to potently neutralize authentic SARS-CoV-2 infection in vitro with half inhibitory concentration (IC50) of 12 ng/mL and effectively treat SARS-CoV-2-infected mice even when administered at as late as 24 h post-infection. We determine an ensemble of cryo-EM structures of 2H2 or 3C1 Fab in complex with the S trimer up to 3.8 Å resolution, revealing the conformational space of the antigen-antibody complexes and MAb-triggered stepwise allosteric rearrangements of the S trimer, delineating a previously uncharacterized dynamic process of coordinated binding of neutralizing antibodies to the trimeric S protein. Our findings provide important information for the development of MAb-based drugs for preventing and treating SARS-CoV-2 infections. | |||||||||
履歴 |
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構造の表示
ムービー |
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構造ビューア | EMマップ: ![]() ![]() ![]() |
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 | ![]() | 26.6 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 16.1 KB 16.1 KB | 表示 表示 | ![]() |
画像 | ![]() | 112.4 KB | ||
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 | ![]() 7dccMC ![]() 7dcxC ![]() 7dd2C ![]() 7dd8C ![]() 7dddC ![]() 7ddnC ![]() 7dk4C ![]() 7dk5C ![]() 7dk6C ![]() 7dk7C 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 |
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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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ボクセルのサイズ | X=Y=Z: 1.02 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
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試料の構成要素
-全体 : Complex of SARC-CoV2-S protein with 3C1 fab, all the three RBDs a...
全体 | 名称: Complex of SARC-CoV2-S protein with 3C1 fab, all the three RBDs are in the up conformation and each of them associates with a 3C1 Fab |
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要素 |
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-超分子 #1: Complex of SARC-CoV2-S protein with 3C1 fab, all the three RBDs a...
超分子 | 名称: Complex of SARC-CoV2-S protein with 3C1 fab, all the three RBDs are in the up conformation and each of them associates with a 3C1 Fab 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: ![]() ![]() |
-超分子 #2: 3C1 fab with a heavy chain and a light chain
超分子 | 名称: 3C1 fab with a heavy chain and a light chain / タイプ: complex / ID: 2 / 親要素: 1 / 含まれる分子: #1, #3 |
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由来(天然) | 生物種: ![]() ![]() |
-超分子 #3: SARC-CoV2-S protein
超分子 | 名称: SARC-CoV2-S protein / タイプ: complex / ID: 3 / 親要素: 1 / 含まれる分子: #2 |
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-分子 #1: The heavy chain of 3C1 fab
分子 | 名称: The heavy chain of 3C1 fab / タイプ: protein_or_peptide / ID: 1 / コピー数: 3 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 24.151785 KDa |
配列 | 文字列: EVQLQESGPS LVKPSQTLSL TCSVTGDSIT NGYWNWIRKF PGNKLEYMGY ISYSGSTYYS PSLKSRISIT RDTSKNQHYL QLNSVTSED TATYYCASDY HGSKYYFDYW GQGTTLTVSS AKTTPPSVYP LAPGSAAQTN SMVTLGCLVK GYFPEPVTVT W NSGSLSSG ...文字列: EVQLQESGPS LVKPSQTLSL TCSVTGDSIT NGYWNWIRKF PGNKLEYMGY ISYSGSTYYS PSLKSRISIT RDTSKNQHYL QLNSVTSED TATYYCASDY HGSKYYFDYW GQGTTLTVSS AKTTPPSVYP LAPGSAAQTN SMVTLGCLVK GYFPEPVTVT W NSGSLSSG VHTFPAVLQS DLYTLSSSVT VPSSTWPSET VTCNVAHPAS STKVDKKIVP RDCG |
-分子 #2: Spike glycoprotein
分子 | 名称: Spike glycoprotein / タイプ: protein_or_peptide / ID: 2 / コピー数: 3 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 140.055906 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHAIHV SGTNGTKRFD NPVLPFNDG VYFASTEKSN IIRGWIFGTT LDSKTQSLLI VNNATNVVIK VCEFQFCNDP FLGVYYHKNN KSWMESEFRV Y SSANNCTF ...文字列: MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHAIHV SGTNGTKRFD NPVLPFNDG VYFASTEKSN IIRGWIFGTT LDSKTQSLLI VNNATNVVIK VCEFQFCNDP FLGVYYHKNN KSWMESEFRV Y SSANNCTF EYVSQPFLMD LEGKQGNFKN LREFVFKNID GYFKIYSKHT PINLVRDLPQ GFSALEPLVD LPIGINITRF QT LLALHRS YLTPGDSSSG WTAGAAAYYV GYLQPRTFLL KYNENGTITD AVDCALDPLS ETKCTLKSFT VEKGIYQTSN FRV QPTESI VRFPNITNLC PFGEVFNATR FASVYAWNRK RISNCVADYS VLYNSASFST FKCYGVSPTK LNDLCFTNVY ADSF VIRGD EVRQIAPGQT GKIADYNYKL PDDFTGCVIA WNSNNLDSKV GGNYNYLYRL FRKSNLKPFE RDISTEIYQA GSTPC NGVE GFNCYFPLQS YGFQPTNGVG YQPYRVVVLS FELLHAPATV CGPKKSTNLV KNKCVNFNFN GLTGTGVLTE SNKKFL PFQ QFGRDIADTT DAVRDPQTLE ILDITPCSFG GVSVITPGTN TSNQVAVLYQ DVNCTEVPVA IHADQLTPTW RVYSTGS NV FQTRAGCLIG AEHVNNSYEC DIPIGAGICA SYQTQTNSPG SASSVASQSI IAYTMSLGAE NSVAYSNNSI AIPTNFTI S VTTEILPVSM TKTSVDCTMY ICGDSTECSN LLLQYGSFCT QLNRALTGIA VEQDKNTQEV FAQVKQIYKT PPIKDFGGF NFSQILPDPS KPSKRSFIED LLFNKVTLAD AGFIKQYGDC LGDIAARDLI CAQKFNGLTV LPPLLTDEMI AQYTSALLAG TITSGWTFG AGAALQIPFA MQMAYRFNGI GVTQNVLYEN QKLIANQFNS AIGKIQDSLS STASALGKLQ DVVNQNAQAL N TLVKQLSS NFGAISSVLN DILSRLDPPE AEVQIDRLIT GRLQSLQTYV TQQLIRAAEI RASANLAATK MSECVLGQSK RV DFCGKGY HLMSFPQSAP HGVVFLHVTY VPAQEKNFTT APAICHDGKA HFPREGVFVS NGTHWFVTQR NFYEPQIITT DNT FVSGNC DVVIGIVNNT VYDPLQPELD SFKEELDKYF KNHTSPDVDL GDISGINASV VNIQKEIDRL NEVAKNLNES LIDL QELGK YEQGSGYIPE APRDGQAYVR KDGEWVLLST FLENLYFQGD YKDDDDKHHH HHHHHH |
-分子 #3: The light chain of 3C1 fab
分子 | 名称: The light chain of 3C1 fab / タイプ: protein_or_peptide / ID: 3 / コピー数: 3 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 23.89133 KDa |
配列 | 文字列: DIVMTQSHKF MSTSVGHRVS ITCKASQDVG NDVAWYQQKP GQSPKLLIYW ASTRHTGVPD RFTGSGSGTD FTLTISNVQS EDLADYFCQ QYNRYPYTFG GGTKLEIKRA DAAPTVSIFP PSSEQLTSGG ASVVCFLNNF YPKDINVKWK IDGSERQNGV L NSWTDQDS ...文字列: DIVMTQSHKF MSTSVGHRVS ITCKASQDVG NDVAWYQQKP GQSPKLLIYW ASTRHTGVPD RFTGSGSGTD FTLTISNVQS EDLADYFCQ QYNRYPYTFG GGTKLEIKRA DAAPTVSIFP PSSEQLTSGG ASVVCFLNNF YPKDINVKWK IDGSERQNGV L NSWTDQDS KDSTYSMSST LTLTKDEYER HNSYTCEATH KTSTSPIVKS FNRNEC |
-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 構成要素:
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グリッド | モデル: Quantifoil / 材質: COPPER / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY / 前処理 - タイプ: GLOW DISCHARGE 詳細: To handle the potential preferred orientation problem, for sample frozen using holey carbon grid, 0.05% Octyl beta-D-glucopyranoside (Sigma) or 0.1% polylysine (Polysciences) was added into ...詳細: To handle the potential preferred orientation problem, for sample frozen using holey carbon grid, 0.05% Octyl beta-D-glucopyranoside (Sigma) or 0.1% polylysine (Polysciences) was added into the sample or applied on grid before freezing, respectively. | ||||||||||||
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 K2 SUMMIT (4k x 4k) 検出モード: SUPER-RESOLUTION / 平均露光時間: 6.45 sec. / 平均電子線量: 49.6 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: FLOOD BEAM / 撮影モード: BRIGHT FIELD |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 4.3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 71057 |
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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 |