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基本情報
登録情報 | データベース: EMDB / ID: EMD-25209 | |||||||||
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タイトル | Structure of human SARS-CoV-2 neutralizing antibody C1C-A3 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 / host cell endoplasmic reticulum-Golgi intermediate compartment membrane ...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 / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / entry receptor-mediated virion attachment to host cell / 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 / 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 | |||||||||
![]() | Pan J / Abraham J / Yang P / Shankar S | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural basis for continued antibody evasion by the SARS-CoV-2 receptor binding domain. 著者: Katherine G Nabel / Sarah A Clark / Sundaresh Shankar / Junhua Pan / Lars E Clark / Pan Yang / Adrian Coscia / Lindsay G A McKay / Haley H Varnum / Vesna Brusic / Nicole V Tolan / Guohai Zhou ...著者: Katherine G Nabel / Sarah A Clark / Sundaresh Shankar / Junhua Pan / Lars E Clark / Pan Yang / Adrian Coscia / Lindsay G A McKay / Haley H Varnum / Vesna Brusic / Nicole V Tolan / Guohai Zhou / Michaël Desjardins / Sarah E Turbett / Sanjat Kanjilal / Amy C Sherman / Anand Dighe / Regina C LaRocque / Edward T Ryan / Casey Tylek / Joel F Cohen-Solal / Anhdao T Darcy / Davide Tavella / Anca Clabbers / Yao Fan / Anthony Griffiths / Ivan R Correia / Jane Seagal / Lindsey R Baden / Richelle C Charles / Jonathan Abraham / ![]() ![]() 要旨: Many studies have examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity after they have become dominant strains. Here, we ...Many studies have examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity after they have become dominant strains. Here, we evaluate the consequences of further viral evolution. We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. We identify an antibody that binds the RBD core to neutralize pseudotypes for all tested variants but show that the RBD can acquire an N-linked glycan to escape neutralization. Our findings portend continued emergence of escape variants as SARS-CoV-2 adapts to humans. | |||||||||
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: ![]() ![]() ![]() |
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マップデータ | ![]() | 49.2 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 23.9 KB 23.9 KB | 表示 表示 | ![]() |
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-検証レポート
文書・要旨 | ![]() | 478.8 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 478.4 KB | 表示 | |
XML形式データ | ![]() | 5.6 KB | 表示 | |
CIF形式データ | ![]() | 6.4 KB | 表示 | |
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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: 0.825 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 : SARS-CoV-2_Hexapro in complex with neutralizing antibody C1C-A3 F...
全体 | 名称: SARS-CoV-2_Hexapro in complex with neutralizing antibody C1C-A3 Fab from human patient |
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要素 |
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-超分子 #1: SARS-CoV-2_Hexapro in complex with neutralizing antibody C1C-A3 F...
超分子 | 名称: SARS-CoV-2_Hexapro in complex with neutralizing antibody C1C-A3 Fab from human patient タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all 詳細: concentration of the SARS-CoV-2 spike protein SARS-CoV-2 Hexapro (trimeric) and human patient antibody C1C-A3 Fab is 0.6 and 0.3 mg/mL in the final complex sample in buffer consisting of 150 ...詳細: concentration of the SARS-CoV-2 spike protein SARS-CoV-2 Hexapro (trimeric) and human patient antibody C1C-A3 Fab is 0.6 and 0.3 mg/mL in the final complex sample in buffer consisting of 150 mM NaCl and 25 mM Tris-HCl, pH 7.5. structure deposited here is one receptor binding domain (RBD) in complex with on C1C-A3 Fab determined from the relate wwPDB deposit D_1000258559. |
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由来(天然) | 生物種: ![]() ![]() 株: isolate Wuhan-Hu-1 |
組換発現 | 生物種: ![]() |
分子量 | 理論値: 50 KDa |
-超分子 #2: SARS-CoV-2 spike protein SARS-CoV-2 Hexapro
超分子 | 名称: SARS-CoV-2 spike protein SARS-CoV-2 Hexapro / タイプ: complex / ID: 2 / 親要素: 1 / 含まれる分子: #1 |
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由来(天然) | 生物種: ![]() ![]() 株: isolate Wuhan-Hu-1 |
組換発現 | 生物種: ![]() |
-超分子 #3: C1C-A3 Fab
超分子 | 名称: C1C-A3 Fab / タイプ: complex / ID: 3 / 親要素: 1 / 含まれる分子: #2-#3 詳細: Fab of C1C-A3 antibody recombinantly expressed using sequence sequenced from single B cells from human patient peripheral blood sample |
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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 詳細: Severe acute respiratory syndrome coronavirus 2 surface glycoprotein (residues 1-1208) of GeneBank locus QHD43416.1 (amino acids 1-15 are the endogenous signal peptide, 16-1208 are SARS-CoV-2 ...詳細: Severe acute respiratory syndrome coronavirus 2 surface glycoprotein (residues 1-1208) of GeneBank locus QHD43416.1 (amino acids 1-15 are the endogenous signal peptide, 16-1208 are SARS-CoV-2 spike protein residues 16-1208, 1209-1210+1237-1239+1255-1258 are linkers, 1211-1236 are T4 fibritinn foldon, 1240-1254 are the avi-tag for biotinylation, 1259-1265 are the TEV protease cleavage site, 1266-1273 are the 8xHis tag; mutations include R682G, R683S, R685S, F817P, A892P, A899P, A942P, K986P, V987P) 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: 141.192203 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 KPSKRSPIED LLFNKVTLAD AGFIKQYGDC LGDIAARDLI CAQKFNGLTV LPPLLTDEMI AQYTSALLAG TITSGWTFG AGPALQIPFP MQMAYRFNGI GVTQNVLYEN QKLIANQFNS AIGKIQDSLS STPSALGKLQ 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 YEQSGYIPEA PRDGQAYVRK DGEWVLLSTF LSAGGLNDIF EAQKIEWHEG ASGENLYFQG HHHHHHHH |
-分子 #2: neutralizing antibody C1C-A3 Fab heavy chain
分子 | 名称: neutralizing antibody C1C-A3 Fab heavy chain / タイプ: protein_or_peptide / ID: 2 詳細: amino acids 1-20 are the human tPA signal peptide, 21-22 are a linker, 23-250 are the C1C-A3 Fab heavy chain residues 1-213 (note insertions in CDR loops; numbering should be according to the PDB file). 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: 27.022607 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MKRGLCCVLL LCGAVFVSPS ASQVQLVESG GGVVQPGRSL RLSCAASGFT FSSYGMHWVR QAPGKGLEWV AVIWYDGTNT YYADSVKGR FTISRDNSKN TLYLQMNSLR AEDTAVYYCA RDLAYRDYVW RYFDLWGRGT LVTVSGASTK GPSVFPLAPS S KSTSGGTA ...文字列: MKRGLCCVLL LCGAVFVSPS ASQVQLVESG GGVVQPGRSL RLSCAASGFT FSSYGMHWVR QAPGKGLEWV AVIWYDGTNT YYADSVKGR FTISRDNSKN TLYLQMNSLR AEDTAVYYCA RDLAYRDYVW RYFDLWGRGT LVTVSGASTK GPSVFPLAPS S KSTSGGTA ALGCLVKDYF PEPVTVSWNS GALTSGVHTF PAVLQSSGLY SLSSVVTVPS SSLGTQTYIC NVNHKPSNTK VD KRVEPKS CDR |
-分子 #3: neutralizing antibody C1C-A3 Fab light chain
分子 | 名称: neutralizing antibody C1C-A3 Fab light chain / タイプ: protein_or_peptide / ID: 3 詳細: amino acids 1-20 are the human tPA signal peptide, 21-22 are a linker, 23-238 are the C1C-A3 Fab light chain residues 1-212 (note insertions in CDR loops; numbering should be according to the PDB file). 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: 25.896107 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MKRGLCCVLL LCGAVFVSPS ASEIVLTQSP ATLSLSPGER ATLSCRASQS VSTYLAWYQQ KFGQAPRLLI YDASNRATGI PARFSGSGS GTDFTLTISS LEPEDFAVYY CQCRSNWPPG ITFGQGTRLE IKRTVAAPSV FIFPPSDEQL KSGTASVVCL L NNFYPREA ...文字列: MKRGLCCVLL LCGAVFVSPS ASEIVLTQSP ATLSLSPGER ATLSCRASQS VSTYLAWYQQ KFGQAPRLLI YDASNRATGI PARFSGSGS GTDFTLTISS LEPEDFAVYY CQCRSNWPPG ITFGQGTRLE IKRTVAAPSV FIFPPSDEQL KSGTASVVCL L NNFYPREA KVQWKVDNAL QSGNSQESVT EQDSKDSTYS LSSTLTLSKA DYEKHKVYAC EVTHQGLSSP VTKSFNRGEC |
-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
濃度 | 0.9 mg/mL | |||||||||
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緩衝液 | pH: 7.5 構成要素:
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グリッド | モデル: Quantifoil R1.2/1.3 / 材質: COPPER / メッシュ: 300 / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: CONTINUOUS / 支持フィルム - Film thickness: 2.0 nm / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 雰囲気: AIR / 前処理 - 気圧: 0.039 kPa 詳細: Quantifoil Cu 1.2/1.3 2nm carbon 300 mesh grids glowed discharge at 15 mA in Pelco EasiGlow | |||||||||
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 293 K / 装置: FEI VITROBOT MARK IV / 詳細: blot for 4-6 seconds. | |||||||||
詳細 | this sample was monodisperse. |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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温度 | 最低: 77.0 K / 最高: 77.0 K |
撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) デジタル化 - サイズ - 横: 5760 pixel / デジタル化 - サイズ - 縦: 4092 pixel / デジタル化 - サンプリング間隔: 5.0 µm / 撮影したグリッド数: 1 / 実像数: 4583 / 平均露光時間: 1.9 sec. / 平均電子線量: 56.5 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | C2レンズ絞り径: 50.0 µm / 倍率(補正後): 60606 / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm / 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 / 倍率(公称値): 105000 |
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 |