+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-37702 | |||||||||
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タイトル | Cryo-EM structure of SARS-CoV-2 Omicron BA.4/5 RBD in complex with rabbit ACE2 (local refinement) | |||||||||
マップデータ | Sharp map of SARS-CoV-2 Omicron BA.4/5 spike protein in complex with rabbit ACE2 | |||||||||
試料 |
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キーワード | Severe acute respiratory syndrome coronavirus 2 / Angiotensin-converting enzyme 2 / Spike protein / VIRAL PROTEIN | |||||||||
機能・相同性 | 機能・相同性情報 加水分解酵素; プロテアーゼ; ペプチド結合加水分解酵素 / positive regulation of L-proline import across plasma membrane / angiotensin-mediated drinking behavior / tryptophan transport / positive regulation of gap junction assembly / regulation of cardiac conduction / peptidyl-dipeptidase activity / carboxypeptidase activity / positive regulation of cardiac muscle contraction / brush border 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 / positive regulation of L-proline import across plasma membrane / angiotensin-mediated drinking behavior / tryptophan transport / positive regulation of gap junction assembly / regulation of cardiac conduction / peptidyl-dipeptidase activity / carboxypeptidase activity / positive regulation of cardiac muscle contraction / brush border membrane / cilium / metallopeptidase activity / virus receptor activity / Maturation of spike protein / viral translation / endopeptidase activity / 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 / apical plasma membrane / 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 / proteolysis / extracellular space / identical protein binding / membrane / metal ion binding / plasma membrane / cytoplasm 類似検索 - 分子機能 | |||||||||
生物種 | Severe acute respiratory syndrome coronavirus 2 (ウイルス) / Oryctolagus cuniculus (ウサギ) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.14 Å | |||||||||
データ登録者 | Li LJ / Shi KY / Yu GH / Gao GF | |||||||||
資金援助 | 中国, 1件
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引用 | ジャーナル: mBio / 年: 2024 タイトル: Structural basis of increased binding affinities of spikes from SARS-CoV-2 Omicron variants to rabbit and hare ACE2s reveals the expanding host tendency. 著者: Kaiyuan Shi / Linjie Li / Chunliang Luo / Zepeng Xu / Baihan Huang / Sufang Ma / Kefang Liu / Guanghui Yu / George F Gao / 要旨: The potential host range of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been expanding alongside its evolution during the pandemic, with rabbits and hares being considered ...The potential host range of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been expanding alongside its evolution during the pandemic, with rabbits and hares being considered important potential hosts, supported by a report of rabbit sero-prevalence in nature. We measured the binding affinities of rabbit and hare angiotensin-converting enzyme 2 (ACE2) with receptor-binding domains (RBDs) from SARS-CoV, SARS-CoV-2, and its variants and found that rabbit and hare ACE2s had broad variant tropism, with significantly enhanced affinities to Omicron BA.4/5 and its subsequent-emerged sub-variants (>10 fold). The structures of rabbit ACE2 complexed with either SARS-CoV-2 prototype (PT) or Omicron BA.4/5 spike (S) proteins were determined, thereby unveiling the importance of rabbit ACE2 Q34 in RBD-interaction and elucidating the molecular basis of the enhanced binding with Omicron BA.4/5 RBD. These results address the highly enhanced risk of rabbits infecting SARS-CoV-2 Omicron sub-variants and the importance of constant surveillance.IMPORTANCEThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has swept the globe and caused immense health and economic damage. SARS-CoV-2 has demonstrated a broad host range, indicating a high risk of interspecies transmission and adaptive mutation. Therefore, constant monitoring for potential hosts is of immense importance. In this study, we found that Omicron BA.4/5 and subsequent-emerged sub-variants exhibited enhanced binding to both rabbit and hare angiotensin-converting enzyme 2 (ACE2), and we elucidated the structural mechanism of their recognition. From the structure, we found that Q34, a unique residue of rabbit ACE2 compared to other ACE2 orthologs, plays an important role in ACE2 recognition. These results address the probability of rabbits/hares being potential hosts of SARS-CoV-2 and broaden our knowledge regarding the molecular mechanism of SARS-CoV-2 interspecies transmission. | |||||||||
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_37702.map.gz | 720.5 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-37702-v30.xml emd-37702.xml | 16.2 KB 16.2 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_37702.png | 87.3 KB | ||
Filedesc metadata | emd-37702.cif.gz | 6 KB | ||
その他 | emd_37702_half_map_1.map.gz emd_37702_half_map_2.map.gz | 764.2 MB 764.2 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-37702 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-37702 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_37702_validation.pdf.gz | 748.2 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_37702_full_validation.pdf.gz | 747.8 KB | 表示 | |
XML形式データ | emd_37702_validation.xml.gz | 20.4 KB | 表示 | |
CIF形式データ | emd_37702_validation.cif.gz | 24.4 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-37702 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-37702 | HTTPS FTP |
-関連構造データ
関連構造データ | 8woyMC 8woxC 8wozC 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 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-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_37702.map.gz / 形式: CCP4 / 大きさ: 824 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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注釈 | Sharp map of SARS-CoV-2 Omicron BA.4/5 spike protein in complex with rabbit ACE2 | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.88 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: Half A map of SARS-CoV-2 Omicron BA.4/5 spike...
ファイル | emd_37702_half_map_1.map | ||||||||||||
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注釈 | Half A map of SARS-CoV-2 Omicron BA.4/5 spike protein in complex with rabbit ACE2 | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: Half B map of SARS-CoV-2 Omicron BA.4/5 spike...
ファイル | emd_37702_half_map_2.map | ||||||||||||
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注釈 | Half B map of SARS-CoV-2 Omicron BA.4/5 spike protein in complex with rabbit ACE2 | ||||||||||||
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 : Cryo-EM structure of SARS-CoV-2 Omicron BA.4/5 RBD in complex wit...
全体 | 名称: Cryo-EM structure of SARS-CoV-2 Omicron BA.4/5 RBD in complex with rabbit ACE2 (local refinement) |
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要素 |
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-超分子 #1: Cryo-EM structure of SARS-CoV-2 Omicron BA.4/5 RBD in complex wit...
超分子 | 名称: Cryo-EM structure of SARS-CoV-2 Omicron BA.4/5 RBD in complex with rabbit ACE2 (local refinement) タイプ: complex / 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: Severe acute respiratory syndrome coronavirus 2 (ウイルス) |
-分子 #1: Angiotensin-converting enzyme
分子 | 名称: Angiotensin-converting enzyme / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO EC番号: 加水分解酵素; プロテアーゼ; ペプチド結合加水分解酵素 |
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由来(天然) | 生物種: Oryctolagus cuniculus (ウサギ) |
分子量 | 理論値: 69.017414 KDa |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: STIEELAKTF LEKFNQEAED LSYQSALASW DYNTNITEEN VQKMNDAEAK WSAFYEEQSK LAKTYPSQEV QNLTVKRQLQ ALQQSGSSA LSADKSKQLN TILSTMSTIY STGKVCNQSN PQECFLLEPG LDEIMAKSTD YNERLWAWEG WRSVVGKQLR P LYEEYVVL ...文字列: STIEELAKTF LEKFNQEAED LSYQSALASW DYNTNITEEN VQKMNDAEAK WSAFYEEQSK LAKTYPSQEV QNLTVKRQLQ ALQQSGSSA LSADKSKQLN TILSTMSTIY STGKVCNQSN PQECFLLEPG LDEIMAKSTD YNERLWAWEG WRSVVGKQLR P LYEEYVVL KNEMARANNY EDYGDYWRAD YEAEGADGYD YSRSQLIDDV ERTFSEIKPL YEQLHAFVRT KLMDAYPSRI SP TGCLPAH LLGDMWGRFW TNLYSLTVPF GQKPNIDVTD TMVNQGWDAE RIFKEAEKFF VSVGLPSMTQ GFWENSMLTE PGD GRKVVC HPTAWDLGKG DFRIKMCTKV TMDNFLTAHH EMGHIQYDMA YATQPFLLRN GANEGFHEAV GEIMSLSAAT PEHL KSIGL LPYDFHEDNE TEINFLLKQA LTIVGTLPFT YMLEKWRWMV FKGEIPKEQW MQKWWEMKRE IVGVVEPMPH DETYC DPAA LFHVANDYSF IRYYTRTIYQ FQFQEALCQA AQHEGPLHKC DISNSTEAGQ KLLNMLRLGR SEPWTLALEN VVGAKN MDV RPLLNYFEPL FTWLKEQNRN SFVGWSTEWT PYA UniProtKB: Angiotensin-converting enzyme |
-分子 #2: Spike protein S1
分子 | 名称: Spike protein S1 / 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: Severe acute respiratory syndrome coronavirus 2 (ウイルス) |
分子量 | 理論値: 26.084525 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: RVQPTESIVR FPNITNLCPF DEVFNATRFA SVYAWNRKRI SNCVADYSVL YNFAPFFAFK CYGVSPTKLN DLCFTNVYAD SFVIRGNEV SQIAPGQTGN IADYNYKLPD DFTGCVIAWN SNKLDSKVGG NYNYRYRLFR KSNLKPFERD ISTEIYQAGN K PCNGVAGV ...文字列: RVQPTESIVR FPNITNLCPF DEVFNATRFA SVYAWNRKRI SNCVADYSVL YNFAPFFAFK CYGVSPTKLN DLCFTNVYAD SFVIRGNEV SQIAPGQTGN IADYNYKLPD DFTGCVIAWN SNKLDSKVGG NYNYRYRLFR KSNLKPFERD ISTEIYQAGN K PCNGVAGV NCYFPLQSYG FRPTYGVGHQ PYRVVVLSFE LLHAPATVCG PKKSTNLVKN KCVNFHHHHH H UniProtKB: Spike glycoprotein |
-分子 #3: ZINC ION
分子 | 名称: ZINC ION / タイプ: ligand / ID: 3 / コピー数: 1 / 式: ZN |
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分子量 | 理論値: 65.409 Da |
-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: 1 / 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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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: 8 |
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凍結 | 凍結剤: ETHANE |
-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: 50.0 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: OTHER / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2.0 µm / 最小 デフォーカス(公称値): 1.0 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
初期モデル | モデルのタイプ: NONE |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.14 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 317529 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |