+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-15588 | |||||||||
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タイトル | BA.4/5 SARS-CoV-2 Spike bound to human ACE2 (local) | |||||||||
マップデータ | b4h | |||||||||
試料 |
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機能・相同性 | 機能・相同性情報 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 / negative regulation of signaling receptor activity / regulation of vasoconstriction ...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 / negative regulation of signaling receptor activity / 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 / positive regulation of cardiac muscle contraction / regulation of cytokine production / viral life cycle / blood vessel diameter maintenance / negative regulation of smooth muscle cell proliferation / brush border membrane / regulation of transmembrane transporter activity / cilium / negative regulation of ERK1 and ERK2 cascade / virion component / metallopeptidase activity / positive regulation of reactive oxygen species metabolic process / endocytic vesicle membrane / virus receptor activity / regulation of inflammatory response / regulation of cell population proliferation / endopeptidase activity / Potential therapeutics for SARS / 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 / apical plasma membrane / symbiont entry into host cell / membrane raft / 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 | Severe acute respiratory syndrome coronavirus 2 (ウイルス) / Homo sapiens (ヒト) / Enterobacteria phage T4 (ファージ) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.92 Å | |||||||||
データ登録者 | Lau K / Ni D / Beckert B / Nazarov S / Myasnikov A / Pojer F / Stahlberg H / Uchikawa E | |||||||||
資金援助 | スイス, 1件
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引用 | ジャーナル: PLoS Pathog / 年: 2023 タイトル: Cryo-EM structures and binding of mouse and human ACE2 to SARS-CoV-2 variants of concern indicate that mutations enabling immune escape could expand host range. 著者: Dongchun Ni / Priscilla Turelli / Bertrand Beckert / Sergey Nazarov / Emiko Uchikawa / Alexander Myasnikov / Florence Pojer / Didier Trono / Henning Stahlberg / Kelvin Lau / 要旨: Investigation of potential hosts of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is crucial to understanding future risks of spillover and spillback. SARS-CoV-2 has been reported ...Investigation of potential hosts of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is crucial to understanding future risks of spillover and spillback. SARS-CoV-2 has been reported to be transmitted from humans to various animals after requiring relatively few mutations. There is significant interest in describing how the virus interacts with mice as they are well adapted to human environments, are used widely as infection models and can be infected. Structural and binding data of the mouse ACE2 receptor with the Spike protein of newly identified SARS-CoV-2 variants are needed to better understand the impact of immune system evading mutations present in variants of concern (VOC). Previous studies have developed mouse-adapted variants and identified residues critical for binding to heterologous ACE2 receptors. Here we report the cryo-EM structures of mouse ACE2 bound to trimeric Spike ectodomains of four different VOC: Beta, Omicron BA.1, Omicron BA.2.12.1 and Omicron BA.4/5. These variants represent the oldest to the newest variants known to bind the mouse ACE2 receptor. Our high-resolution structural data complemented with bio-layer interferometry (BLI) binding assays reveal a requirement for a combination of mutations in the Spike protein that enable binding to the mouse ACE2 receptor. #1: ジャーナル: Biorxiv / 年: 2023 タイトル: Cryo-EM structures and binding of mouse and human ACE2 to SARS-CoV-2 variants of concern indicate that mutations enabling immune escape could expand host range 著者: Ni D / Turelli P / Beckert B / Nazarov S / Uchikawa E / Myasnikov A / Pojer F / Trono D / Stahlberg H / Lau K | |||||||||
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_15588.map.gz | 168.1 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-15588-v30.xml emd-15588.xml | 20.2 KB 20.2 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_15588_fsc.xml | 11.9 KB | 表示 | FSCデータファイル |
画像 | emd_15588.png | 76 KB | ||
その他 | emd_15588_half_map_1.map.gz emd_15588_half_map_2.map.gz | 165.1 MB 165.1 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-15588 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-15588 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_15588_validation.pdf.gz | 1.1 MB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_15588_full_validation.pdf.gz | 1.1 MB | 表示 | |
XML形式データ | emd_15588_validation.xml.gz | 20.4 KB | 表示 | |
CIF形式データ | emd_15588_validation.cif.gz | 26.6 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-15588 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-15588 | HTTPS FTP |
-関連構造データ
-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_15588.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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注釈 | b4h | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.0144 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
-ハーフマップ: b4h
ファイル | emd_15588_half_map_1.map | ||||||||||||
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注釈 | b4h | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: b4h
ファイル | emd_15588_half_map_2.map | ||||||||||||
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注釈 | b4h | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
-全体 : BA.4/5 SARS-CoV-2 Spike bound to human ACE2 (local)
全体 | 名称: BA.4/5 SARS-CoV-2 Spike bound to human ACE2 (local) |
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要素 |
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-超分子 #1: BA.4/5 SARS-CoV-2 Spike bound to human ACE2 (local)
超分子 | 名称: BA.4/5 SARS-CoV-2 Spike bound to human ACE2 (local) / タイプ: complex / ID: 1 / キメラ: Yes / 親要素: 0 / 含まれる分子: #1-#2 |
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分子量 | 理論値: 430 KDa |
-超分子 #2: SARS-CoV-2 BA.4/5 spike protein
超分子 | 名称: SARS-CoV-2 BA.4/5 spike protein / タイプ: complex / ID: 2 / キメラ: Yes / 親要素: 1 / 含まれる分子: #1 |
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由来(天然) | 生物種: Severe acute respiratory syndrome coronavirus 2 (ウイルス) |
-超分子 #3: Human ACE2
超分子 | 名称: Human ACE2 / タイプ: complex / ID: 3 / キメラ: Yes / 親要素: 1 / 含まれる分子: #2 |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Spike glycoprotein,Fibritin
分子 | 名称: Spike glycoprotein,Fibritin / 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: Enterobacteria phage T4 (ファージ) |
分子量 | 理論値: 142.688062 KDa |
組換発現 | 生物種: Cricetulus griseus (モンゴルキヌゲネズミ) |
配列 | 文字列: MFVFLVLLPL VSSQCVNLIT RTQLPPSYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHAIHV SGTNGTKRFD NPVLPFNDG VYFASTEKSN IIRGWIFGTT LDSKTQSLLI VNNATNVVIK VCEFQFCNDP FLDVYYHKNN KSWMESEFRV Y SSANNCTF ...文字列: MFVFLVLLPL VSSQCVNLIT RTQLPPSYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHAIHV SGTNGTKRFD NPVLPFNDG VYFASTEKSN IIRGWIFGTT LDSKTQSLLI VNNATNVVIK VCEFQFCNDP FLDVYYHKNN KSWMESEFRV Y SSANNCTF EYVSQPFLMD LEGKQGNFKN LREFVFKNID GYFKIYSKHT PINLGRDLPQ GFSALEPLVD LPIGINITRF QT LLALHRS YLTPGDSSSG WTAGAAAYYV GYLQPRTFLL KYNENGTITD AVDCALDPLS ETKCTLKSFT VEKGIYQTSN FRV QPTESI VRFPNITNLC PFDEVFNATR FASVYAWNRK RISNCVADYS VLYNFAPFFA FKCYGVSPTK LNDLCFTNVY ADSF VIRGN EVSQIAPGQT GNIADYNYKL PDDFTGCVIA WNSNKLDSKV GGNYNYRYRL FRKSNLKPFE RDISTEIYQA GNKPC NGVA GVNCYFPLQS YGFRPTYGVG HQPYRVVVLS FELLHAPATV CGPKKSTNLV KNKCVNFNFN GLTGTGVLTE SNKKFL PFQ QFGRDIADTT DAVRDPQTLE ILDITPCSFG GVSVITPGTN TSNQVAVLYQ GVNCTEVPVA IHADQLTPTW RVYSTGS NV FQTRAGCLIG AEYVNNSYEC DIPIGAGICA SYQTQTKSHG SASSVASQSI IAYTMSLGAE NSVAYSNNSI AIPTNFTI S VTTEILPVSM TKTSVDCTMY ICGDSTECSN LLLQYGSFCT QLKRALTGIA VEQDKNTQEV FAQVKQIYKT PPIKYFGGF NFSQILPDPS KPSKRSFIED LLFNKVTLAD AGFIKQYGDC LGDIAARDLI CAQKFNGLTV LPPLLTDEMI AQYTSALLAG TITSGWTFG AGAALQIPFA MQMAYRFNGI GVTQNVLYEN QKLIANQFNS AIGKIQDSLS STASALGKLQ DVVNHNAQAL N TLVKQLSS KFGAISSVLN 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 FLGRSLEVLF QGPGHHHHHH HHSAWSHPQF EKGGGSGGGG SGGSA WSHP QFEK |
-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: 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: 101.94132 KDa |
組換発現 | 生物種: Cricetulus griseus (モンゴルキヌゲネズミ) |
配列 | 文字列: MGTLSAPPCT QRIKWKGLLL TASLLNFWNL PTTASTIEEQ AKTFLDKFNH EAEDLFYQSS LASWNYNTNI TEENVQNMNN AGDKWSAFL KEQSTLAQMY PLQEIQNLTV KLQLQALQQN GSSVLSEDKS KRLNTILNTM STIYSTGKVC NPDNPQECLL L EPGLNEIM ...文字列: MGTLSAPPCT QRIKWKGLLL TASLLNFWNL PTTASTIEEQ AKTFLDKFNH EAEDLFYQSS LASWNYNTNI TEENVQNMNN AGDKWSAFL KEQSTLAQMY PLQEIQNLTV KLQLQALQQN GSSVLSEDKS KRLNTILNTM STIYSTGKVC NPDNPQECLL L EPGLNEIM ANSLDYNERL WAWESWRSEV GKQLRPLYEE YVVLKNEMAR ANHYEDYGDY WRGDYEVNGV DGYDYSRGQL IE DVEHTFE EIKPLYEHLH AYVRAKLMNA YPSYISPIGC LPAHLLGDMW GRFWTNLYSL TVPFGQKPNI DVTDAMVDQA WDA QRIFKE AEKFFVSVGL PNMTQGFWEN SMLTDPGNVQ KAVCHPTAWD LGKGDFRILM CTKVTMDDFL TAHHEMGHIQ YDMA YAAQP FLLRNGANEG FHEAVGEIMS LSAATPKHLK SIGLLSPDFQ EDNETEINFL LKQALTIVGT LPFTYMLEKW RWMVF KGEI PKDQWMKKWW EMKREIVGVV EPVPHDETYC DPASLFHVSN DYSFIRYYTR TLYQFQFQEA LCQAAKHEGP LHKCDI SNS TEAGQKLFNM LRLGKSEPWT LALENVVGAK NMNVRPLLNY FEPLFTWLKD QNKNSFVGWS TDWSPYADGS LEVLFQG PM DEPRGPTIKP CPPCKCPAPN LLGGPSVFIF PPKIKDVLMI SLSPIVTCVV VDVSEDDPDV QISWFVNNVE VHTAQTQT H REDYNSTLRV VSALPIQHQD WMSGKEFKCK VNNKDLPAPI ERTISKPKGS VRAPQVYVLP PPEEEMTKKQ VTLTCMVTD FMPEDIYVEW TNNGKTELNY KNTEPVLDSD GSYFMYSKLR VEKKNWVERN SYSCSVVHEG LHNHHTTKSF SRTPGKHHHH HHHHHH |
-分子 #3: 2-acetamido-2-deoxy-beta-D-glucopyranose
分子 | 名称: 2-acetamido-2-deoxy-beta-D-glucopyranose / タイプ: ligand / ID: 3 / コピー数: 6 / 式: NAG |
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分子量 | 理論値: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-分子 #4: ZINC ION
分子 | 名称: ZINC ION / タイプ: ligand / ID: 4 / コピー数: 1 / 式: ZN |
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分子量 | 理論値: 65.409 Da |
-分子 #5: water
分子 | 名称: water / タイプ: ligand / ID: 5 / コピー数: 1 / 式: HOH |
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分子量 | 理論値: 18.015 Da |
Chemical component information | ChemComp-HOH: |
-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: 7.5 |
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凍結 | 凍結剤: ETHANE |
詳細 | BA.4/5 SARS-CoV-2 Spike bound to human ACE2 |
-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: FEI FALCON IV (4k x 4k) 平均電子線量: 58.0 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: 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): 0.8 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |