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基本情報
登録情報 | データベース: EMDB / ID: EMD-30516 | |||||||||
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タイトル | S protein of SARS-CoV-2 in complex bound with P5A-2G9 | |||||||||
![]() | cryo EM map of the S protein of SARS-CoV-2 in complex bound with P5A-2G9 | |||||||||
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機能・相同性 | ![]() CD22 mediated BCR regulation / immunoglobulin complex / Fc epsilon receptor (FCERI) signaling / Classical antibody-mediated complement activation / Initial triggering of complement / FCGR activation / immunoglobulin mediated immune response / Role of phospholipids in phagocytosis / Role of LAT2/NTAL/LAB on calcium mobilization / Scavenging of heme from plasma ...CD22 mediated BCR regulation / immunoglobulin complex / Fc epsilon receptor (FCERI) signaling / Classical antibody-mediated complement activation / Initial triggering of complement / FCGR activation / immunoglobulin mediated immune response / Role of phospholipids in phagocytosis / Role of LAT2/NTAL/LAB on calcium mobilization / Scavenging of heme from plasma / immunoglobulin complex, circulating / immunoglobulin receptor binding / FCERI mediated Ca+2 mobilization / FCGR3A-mediated IL10 synthesis / complement activation, classical pathway / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / Regulation of Complement cascade / antigen binding / Cell surface interactions at the vascular wall / FCERI mediated MAPK activation / FCGR3A-mediated phagocytosis / Regulation of actin dynamics for phagocytic cup formation / FCERI mediated NF-kB activation / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / antibacterial humoral response / 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 / Potential therapeutics for SARS / Induction of Cell-Cell Fusion / blood microparticle / 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 / immune response / 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 / extracellular exosome / extracellular region / 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: 2.7 Å | |||||||||
![]() | Yan RH / Zhang YY / Li YN / Zhou Q | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural basis for bivalent binding and inhibition of SARS-CoV-2 infection by human potent neutralizing antibodies. 著者: Renhong Yan / Ruoke Wang / Bin Ju / Jinfang Yu / Yuanyuan Zhang / Nan Liu / Jia Wang / Qi Zhang / Peng Chen / Bing Zhou / Yaning Li / Yaping Shen / Shuyuan Zhang / Long Tian / Yingying Guo / ...著者: Renhong Yan / Ruoke Wang / Bin Ju / Jinfang Yu / Yuanyuan Zhang / Nan Liu / Jia Wang / Qi Zhang / Peng Chen / Bing Zhou / Yaning Li / Yaping Shen / Shuyuan Zhang / Long Tian / Yingying Guo / Lu Xia / Xinyue Zhong / Lin Cheng / Xiangyang Ge / Juanjuan Zhao / Hong-Wei Wang / Xinquan Wang / Zheng Zhang / Linqi Zhang / Qiang Zhou / ![]() 要旨: Neutralizing monoclonal antibodies (nAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represent promising candidates for clinical intervention against coronavirus disease 2019 ...Neutralizing monoclonal antibodies (nAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represent promising candidates for clinical intervention against coronavirus disease 2019 (COVID-19). We isolated a large number of nAbs from SARS-CoV-2-infected individuals capable of disrupting proper interaction between the receptor binding domain (RBD) of the viral spike (S) protein and the receptor angiotensin converting enzyme 2 (ACE2). However, the structural basis for their potent neutralizing activity remains unclear. Here, we report cryo-EM structures of the ten most potent nAbs in their native full-length IgG-form or in both IgG-form and Fab-form bound to the trimeric S protein of SARS-CoV-2. The bivalent binding of the full-length IgG is found to associate with more RBDs in the "up" conformation than the monovalent binding of Fab, perhaps contributing to the enhanced neutralizing activity of IgG and triggering more shedding of the S1 subunit from the S protein. Comparison of a large number of nAbs identified common and unique structural features associated with their potent neutralizing activities. This work provides a structural basis for further understanding the mechanism of nAbs, especially through revealing the bivalent binding and its correlation with more potent neutralization and the shedding of S1 subunit. | |||||||||
履歴 |
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構造の表示
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構造ビューア | EMマップ: ![]() ![]() ![]() |
添付画像 |
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マップデータ | ![]() | 85.3 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 14.8 KB 14.8 KB | 表示 表示 | ![]() |
画像 | ![]() | 41.2 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 | ![]() 7cztMC ![]() 7czpC ![]() 7czqC ![]() 7czrC ![]() 7czsC ![]() 7czuC ![]() 7czvC ![]() 7czwC ![]() 7czxC ![]() 7czyC ![]() 7czzC ![]() 7d00C ![]() 7d03C ![]() 7d0bC ![]() 7d0cC ![]() 7d0dC 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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注釈 | cryo EM map of the S protein of SARS-CoV-2 in complex bound with P5A-2G9 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.087 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 : S protein of SARS-CoV-2 in complex bound with P2B-2G9
全体 | 名称: S protein of SARS-CoV-2 in complex bound with P2B-2G9 |
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要素 |
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-超分子 #1: S protein of SARS-CoV-2 in complex bound with P2B-2G9
超分子 | 名称: S protein of SARS-CoV-2 in complex bound with P2B-2G9 タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#3 |
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由来(天然) | 生物種: ![]() |
組換発現 | 生物種: ![]() |
-分子 #1: Spike glycoprotein
分子 | 名称: Spike glycoprotein / 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: 142.502594 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 SYQTQTNSPR RARSVASQSI 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 YEQYIKWPWY IWLGFIAGLI AIVMVTIMLC CMTSCCSCLK GCCSCGSCCK FDEDDSEPVL KGVKLHYTLE DYKDD DDK |
-分子 #2: Immunoglobulin heavy variable 3-33,chainH of P5A-2G9,Immunoglobul...
分子 | 名称: Immunoglobulin heavy variable 3-33,chainH of P5A-2G9,Immunoglobulin gamma-1 heavy chain タイプ: protein_or_peptide / ID: 2 / コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 49.457594 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: QVQLVESGGG VVQPGRSLRL SCAASGFTFS SYGMHWVRQA PGKGLEWVAV IWYDGSNKYY ADSVKGRFTI SRDNSKNTLY LQMNSLRAE DTAVYYCARW FHTGGYFDYW GQGTLVTVSS ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS W NSGALTSG ...文字列: QVQLVESGGG VVQPGRSLRL SCAASGFTFS SYGMHWVRQA PGKGLEWVAV IWYDGSNKYY ADSVKGRFTI SRDNSKNTLY LQMNSLRAE DTAVYYCARW FHTGGYFDYW GQGTLVTVSS ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS W NSGALTSG VHTFPAVLQS SGLYSLSSVV TVPSSSLGTQ TYICNVNHKP SNTKVDKKVE PKSCDKTHTC PPCPAPELLG GP SVFLFPP KPKDTLMISR TPEVTCVVVD VSHEDPEVKF NWYVDGVEVH NAKTKPREEQ YNSTYRVVSV LTVLHQDWLN GKE YKCKVS NKALPAPIEK TISKAKGQPR EPQVYTLPPS RDELTKNQVS LTCLVKGFYP SDIAVEWESN GQPENNYKTT PPVL DSDGS FFLYSKLTVD KSRWQQGNVF SCSVMHEALH NHYTQKSLSL SPGK |
-分子 #3: IG c689_light_IGLV5-37_IGLJ3,IGL@ protein
分子 | 名称: IG c689_light_IGLV5-37_IGLJ3,IGL@ protein / タイプ: protein_or_peptide / ID: 3 / コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 23.854383 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: QPVLTQPPSS SASPGESARL TCTLPSDINV SSYNIYWYQQ KPGSPPRYLL YYYSDSDKGQ GSGVPSRFSG SKDASANTGI LLISGLQSE DEADYYCMIW PSNALYVFGT GTKVTVLGQP KAAPSVTLFP PSSEELQANK ATLVCLISDF YPGAVTVAWK A DSSPVKAG ...文字列: QPVLTQPPSS SASPGESARL TCTLPSDINV SSYNIYWYQQ KPGSPPRYLL YYYSDSDKGQ GSGVPSRFSG SKDASANTGI LLISGLQSE DEADYYCMIW PSNALYVFGT GTKVTVLGQP KAAPSVTLFP PSSEELQANK ATLVCLISDF YPGAVTVAWK A DSSPVKAG VETTTPSKQS NNKYAASSYL SLTPEQWKSH RSYSCQVTHE GSTVEKTVAP TECS |
-分子 #5: 2-acetamido-2-deoxy-beta-D-glucopyranose
分子 | 名称: 2-acetamido-2-deoxy-beta-D-glucopyranose / タイプ: ligand / ID: 5 / コピー数: 28 / 式: NAG |
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分子量 | 理論値: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-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: 8 |
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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: FLOOD BEAM / 撮影モード: BRIGHT FIELD |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
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: 2.7 Å / 解像度の算出法: FSC 0.143 CUT-OFF / ソフトウェア - 名称: RELION (ver. 3.0.6) / 使用した粒子像数: 497874 |
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初期 角度割当 | タイプ: ANGULAR RECONSTITUTION |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |