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基本情報
登録情報 | ![]() | |||||||||
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タイトル | Structures of Omicron Spike complexes illuminate broad-spectrum neutralizing antibody development | |||||||||
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機能・相同性 | ![]() positive regulation of amino acid transport / angiotensin-converting enzyme 2 / positive regulation of L-proline import across plasma membrane / 加水分解酵素; プロテアーゼ; ペプチド結合加水分解酵素; 金属プロテアーゼ / angiotensin-mediated drinking behavior / regulation of systemic arterial blood pressure by renin-angiotensin / tryptophan transport / positive regulation of gap junction assembly / regulation of vasoconstriction / regulation of cardiac conduction ...positive regulation of amino acid transport / angiotensin-converting enzyme 2 / positive regulation of L-proline import across plasma membrane / 加水分解酵素; プロテアーゼ; ペプチド結合加水分解酵素; 金属プロテアーゼ / angiotensin-mediated drinking behavior / regulation of systemic arterial blood pressure by renin-angiotensin / tryptophan transport / positive regulation of gap junction assembly / regulation of vasoconstriction / regulation of cardiac conduction / peptidyl-dipeptidase activity / maternal process involved in female pregnancy / angiotensin maturation / Metabolism of Angiotensinogen to Angiotensins / metallocarboxypeptidase activity / carboxypeptidase activity / Attachment and Entry / negative regulation of signaling receptor activity / positive regulation of cardiac muscle contraction / regulation of cytokine production / viral life cycle / blood vessel diameter maintenance / brush border membrane / regulation of transmembrane transporter activity / negative regulation of smooth muscle cell proliferation / negative regulation of ERK1 and ERK2 cascade / cilium / metallopeptidase activity / endocytic vesicle membrane / positive regulation of reactive oxygen species metabolic process / virus receptor activity / regulation of cell population proliferation / regulation of inflammatory response / endopeptidase activity / 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 / structural constituent of virion / entry receptor-mediated virion attachment to host cell / symbiont-mediated suppression of host innate immune response / 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 / host cell surface receptor binding / symbiont entry into host cell / membrane raft / apical plasma membrane / endoplasmic reticulum lumen / 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 / cell surface / extracellular space / zinc ion binding / 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: 3.0 Å | |||||||||
![]() | Guo H / Gao Y / Ji X / Yang H | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structures of Omicron spike complexes and implications for neutralizing antibody development. 著者: Hangtian Guo / Yan Gao / Tinghan Li / Tingting Li / Yuchi Lu / Le Zheng / Yue Liu / Tingting Yang / Feiyang Luo / Shuyi Song / Wei Wang / Xiuna Yang / Henry C Nguyen / Hongkai Zhang / Ailong ...著者: Hangtian Guo / Yan Gao / Tinghan Li / Tingting Li / Yuchi Lu / Le Zheng / Yue Liu / Tingting Yang / Feiyang Luo / Shuyi Song / Wei Wang / Xiuna Yang / Henry C Nguyen / Hongkai Zhang / Ailong Huang / Aishun Jin / Haitao Yang / Zihe Rao / Xiaoyun Ji / ![]() ![]() 要旨: The emergence of the SARS-CoV-2 Omicron variant is dominant in many countries worldwide. The high number of spike mutations is responsible for the broad immune evasion from existing vaccines and ...The emergence of the SARS-CoV-2 Omicron variant is dominant in many countries worldwide. The high number of spike mutations is responsible for the broad immune evasion from existing vaccines and antibody drugs. To understand this, we first present the cryo-electron microscopy structure of ACE2-bound SARS-CoV-2 Omicron spike. Comparison to previous spike antibody structures explains how Omicron escapes these therapeutics. Secondly, we report structures of Omicron, Delta, and wild-type spikes bound to a patient-derived Fab antibody fragment (510A5), which provides direct evidence where antibody binding is greatly attenuated by the Omicron mutations, freeing spike to bind ACE2. Together with biochemical binding and 510A5 neutralization assays, our work establishes principles of binding required for neutralization and clearly illustrates how the mutations lead to antibody evasion yet retain strong ACE2 interactions. Structural information on spike with both bound and unbound antibodies collectively elucidates potential strategies for generation of therapeutic antibodies. | |||||||||
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-検証レポート
文書・要旨 | ![]() | 445.3 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 444.8 KB | 表示 | |
XML形式データ | ![]() | 8 KB | 表示 | |
CIF形式データ | ![]() | 9.2 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 | ![]() 7ws8MC ![]() 7ws0C ![]() 7ws1C ![]() 7ws2C ![]() 7ws3C ![]() 7ws4C ![]() 7ws5C ![]() 7ws6C ![]() 7ws7C ![]() 7ws9C ![]() 7wsaC 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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ボクセルのサイズ | X=Y=Z: 0.832 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
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試料の構成要素
-全体 : SARS-CoV-2 Omicron spike glycoprotein complex with hACE2
全体 | 名称: SARS-CoV-2 Omicron spike glycoprotein complex with hACE2 |
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要素 |
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-超分子 #1: SARS-CoV-2 Omicron spike glycoprotein complex with hACE2
超分子 | 名称: SARS-CoV-2 Omicron spike glycoprotein complex with hACE2 タイプ: complex / キメラ: Yes / ID: 1 / 親要素: 0 / 含まれる分子: #1-#2 |
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由来(天然) | 生物種: ![]() ![]() |
-超分子 #2: Omicron spike glycoprotein trimer
超分子 | 名称: Omicron spike glycoprotein trimer / タイプ: complex / キメラ: Yes / ID: 2 / 親要素: 1 / 含まれる分子: #1 / 詳細: SARS-CoV-2 Omicron variant spike protein |
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由来(天然) | 生物種: ![]() |
組換発現 | 生物種: ![]() |
-超分子 #3: hACE2
超分子 | 名称: hACE2 / タイプ: complex / キメラ: Yes / ID: 3 / 親要素: 1 / 含まれる分子: #2 / 詳細: human angiotensin-converting enzyme 2 PD |
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-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: 133.940031 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHVISG TNGTKRFDNP VLPFNDGVY FASIEKSNII RGWIFGTTLD SKTQSLLIVN NATNVVIKVC EFQFCNDPFL DHKNNKSWME SEFRVYSSAN N CTFEYVSQ ...文字列: MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHVISG TNGTKRFDNP VLPFNDGVY FASIEKSNII RGWIFGTTLD SKTQSLLIVN NATNVVIKVC EFQFCNDPFL DHKNNKSWME SEFRVYSSAN N CTFEYVSQ PFLMDLEGKQ GNFKNLREFV FKNIDGYFKI YSKHTPIIVR EPEDLPQGFS ALEPLVDLPI GINITRFQTL LA LHRSYLT PGDSSSGWTA GAAAYYVGYL QPRTFLLKYN ENGTITDAVD CALDPLSETK CTLKSFTVEK GIYQTSNFRV QPT ESIVRF PNITNLCPFD EVFNATRFAS VYAWNRKRIS NCVADYSVLY NLAPFFTFKC YGVSPTKLND LCFTNVYADS FVIR GDEVR QIAPGQTGNI ADYNYKLPDD FTGCVIAWNS NKLDSKVSGN YNYLYRLFRK SNLKPFERDI STEIYQAGNK PCNGV AGFN CYFPLRSYSF RPTYGVGHQP YRVVVLSFEL LHAPATVCGP KKSTNLVKNK CVNFNFNGLK GTGVLTESNK KFLPFQ QFG RDIADTTDAV RDPQTLEILD ITPCSFGGVS VITPGTNTSN QVAVLYQGVN CTEVPVAIHA DQLTPTWRVY STGSNVF QT RAGCLIGAEY VNNSYECDIP IGAGICASYQ TQTKSHGSAS SVASQSIIAY TMSLGAENSV AYSNNSIAIP TNFTISVT T EILPVSMTKT SVDCTMYICG DSTECSNLLL QYGSFCTQLK RALTGIAVEQ DKNTQEVFAQ VKQIYKTPPI KYFGGFNFS QILPDPSKPS KRSPIEDLLF NKVTLADAGF IKQYGDCLGD IAARDLICAQ KFKGLTVLPP LLTDEMIAQY TSALLAGTIT SGWTFGAGP ALQIPFPMQM AYRFNGIGVT QNVLYENQKL IANQFNSAIG KIQDSLSSTP SALGKLQDVV NHNAQALNTL V KQLSSKFG AISSVLNDIF SRLDPPEAEV QIDRLITGRL QSLQTYVTQQ LIRAAEIRAS ANLAATKMSE CVLGQSKRVD FC GKGYHLM SFPQSAPHGV VFLHVTYVPA QEKNFTTAPA ICHDGKAHFP REGVFVSNGT HWFVTQRNFY EPQIITTDNT FVS GNCDVV IGIVNNTVYD PLQPELDSFK EELDKYFKNH TSPDVDLGDI SGINASVVNI QKEIDRLNEV AKNLNESLID LQEL GKYEQ |
-分子 #2: Processed angiotensin-converting enzyme 2
分子 | 名称: Processed angiotensin-converting enzyme 2 / 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: 68.9675 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: STIEEQAKTF LDKFNHEAED LFYQSSLASW NYNTNITEEN VQNMNNAGDK WSAFLKEQST LAQMYPLQEI QNLTVKLQLQ ALQQNGSSV LSEDKSKRLN TILNTMSTIY STGKVCNPDN PQECLLLEPG LNEIMANSLD YNERLWAWES WRSEVGKQLR P LYEEYVVL ...文字列: STIEEQAKTF LDKFNHEAED LFYQSSLASW NYNTNITEEN VQNMNNAGDK WSAFLKEQST LAQMYPLQEI QNLTVKLQLQ ALQQNGSSV LSEDKSKRLN TILNTMSTIY STGKVCNPDN PQECLLLEPG LNEIMANSLD YNERLWAWES WRSEVGKQLR P LYEEYVVL KNEMARANHY EDYGDYWRGD YEVNGVDGYD YSRGQLIEDV EHTFEEIKPL YEHLHAYVRA KLMNAYPSYI SP IGCLPAH LLGDMWGRFW TNLYSLTVPF GQKPNIDVTD AMVDQAWDAQ RIFKEAEKFF VSVGLPNMTQ GFWENSMLTD PGN VQKAVC HPTAWDLGKG DFRILMCTKV TMDDFLTAHH EMGHIQYDMA YAAQPFLLRN GANEGFHEAV GEIMSLSAAT PKHL KSIGL LSPDFQEDNE TEINFLLKQA LTIVGTLPFT YMLEKWRWMV FKGEIPKDQW MKKWWEMKRE IVGVVEPVPH DETYC DPAS LFHVSNDYSF IRYYTRTLYQ FQFQEALCQA AKHEGPLHKC DISNSTEAGQ KLFNMLRLGK SEPWTLALEN VVGAKN MNV RPLLNYFEPL FTWLKDQNKN SFVGWSTDWS PY |
-分子 #4: 2-acetamido-2-deoxy-beta-D-glucopyranose
分子 | 名称: 2-acetamido-2-deoxy-beta-D-glucopyranose / タイプ: ligand / ID: 4 / コピー数: 20 / 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: 7.4 |
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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 (6k x 4k) / 平均電子線量: 60.0 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): 2.8000000000000003 µm 最小 デフォーカス(公称値): 1.2 µm |
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: 3.0 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 118216 |
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初期 角度割当 | タイプ: COMMON LINE |
最終 角度割当 | タイプ: COMMON LINE |