+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-37703 | |||||||||
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Title | Cryo-EM structure of SARS-CoV RBD in complex with rabbit ACE2 | |||||||||
Map data | Sharp map of SARS-CoV RBD in complex with rabbit ACE2 | |||||||||
Sample |
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Keywords | Severe acute respiratory syndrome coronavirus / Angiotensin-converting enzyme 2 (protein) / rabbit / VIRAL PROTEIN | |||||||||
Function / homology | Function and homology information Maturation of spike protein / Translation of Structural Proteins / Virion Assembly and Release / Hydrolases; Acting on peptide bonds (peptidases) / 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 ...Maturation of spike protein / Translation of Structural Proteins / Virion Assembly and Release / Hydrolases; Acting on peptide bonds (peptidases) / 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 / Attachment and Entry / carboxypeptidase activity / positive regulation of cardiac muscle contraction / brush border membrane / cilium / endocytosis involved in viral entry into host cell / SARS-CoV-1 activates/modulates innate immune responses / metallopeptidase activity / virus receptor activity / endopeptidase activity / suppression by virus of host tetherin activity / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / entry receptor-mediated virion attachment to host cell / membrane fusion / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / 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 / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / host cell plasma membrane / virion membrane / cell surface / proteolysis / extracellular space / membrane / identical protein binding / metal ion binding / cytoplasm Similarity search - Function | |||||||||
Biological species | Severe acute respiratory syndrome coronavirus / Oryctolagus cuniculus (rabbit) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.25 Å | |||||||||
Authors | Li LJ / Shi KY / Yu GH / Gao GF | |||||||||
Funding support | China, 1 items
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Citation | Journal: mBio / Year: 2024 Title: Structural basis of increased binding affinities of spikes from SARS-CoV-2 Omicron variants to rabbit and hare ACE2s reveals the expanding host tendency. Authors: Kaiyuan Shi / Linjie Li / Chunliang Luo / Zepeng Xu / Baihan Huang / Sufang Ma / Kefang Liu / Guanghui Yu / George F Gao / Abstract: 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. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_37703.map.gz | 110 MB | EMDB map data format | |
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Header (meta data) | emd-37703-v30.xml emd-37703.xml | 15.6 KB 15.6 KB | Display Display | EMDB header |
Images | emd_37703.png | 91.3 KB | ||
Filedesc metadata | emd-37703.cif.gz | 5.8 KB | ||
Others | emd_37703_half_map_1.map.gz emd_37703_half_map_2.map.gz | 116.1 MB 116.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-37703 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-37703 | HTTPS FTP |
-Related structure data
Related structure data | 8wozMC 8woxC 8woyC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_37703.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | Sharp map of SARS-CoV RBD in complex with rabbit ACE2 | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.69 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: Half A map of SARS-CoV RBD in complex with rabbit ACE2
File | emd_37703_half_map_1.map | ||||||||||||
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Annotation | Half A map of SARS-CoV RBD in complex with rabbit ACE2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half B map of SARS-CoV RBD in complex with rabbit ACE2
File | emd_37703_half_map_2.map | ||||||||||||
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Annotation | Half B map of SARS-CoV RBD in complex with rabbit ACE2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Cryo-EM structure of SARS-CoV RBD in complex with rabbit ACE2
Entire | Name: Cryo-EM structure of SARS-CoV RBD in complex with rabbit ACE2 |
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Components |
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-Supramolecule #1: Cryo-EM structure of SARS-CoV RBD in complex with rabbit ACE2
Supramolecule | Name: Cryo-EM structure of SARS-CoV RBD in complex with rabbit ACE2 type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus |
-Macromolecule #1: Angiotensin-converting enzyme
Macromolecule | Name: Angiotensin-converting enzyme / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: Hydrolases; Acting on peptide bonds (peptidases) |
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Source (natural) | Organism: Oryctolagus cuniculus (rabbit) |
Molecular weight | Theoretical: 69.846312 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: STIEELAKTF LEKFNQEAED LSYQSALASW DYNTNITEEN VQKMNDAEAK WSAFYEEQSK LAKTYPSQEV QNLTVKRQLQ ALQQSGSSA LSADKSKQLN TILSTMSTIY STGKVCNQSN PQECFLLEPG LDEIMAKSTD YNERLWAWEG WRSVVGKQLR P LYEEYVVL ...String: 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 PYAHHHHHH UniProtKB: Angiotensin-converting enzyme |
-Macromolecule #2: Spike protein S1
Macromolecule | Name: Spike protein S1 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus |
Molecular weight | Theoretical: 25.863234 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: RVVPSGDVVR FPNITNLCPF GEVFNATKFP SVYAWERKKI SNCVADYSVL YNSTFFSTFK CYGVSATKLN DLCFSNVYAD SFVVKGDDV RQIAPGQTGV IADYNYKLPD DFMGCVLAWN TRNIDATSTG NYNYKYRYLR HGKLRPFERD ISNVPFSPDG K PCTPPALN ...String: RVVPSGDVVR FPNITNLCPF GEVFNATKFP SVYAWERKKI SNCVADYSVL YNSTFFSTFK CYGVSATKLN DLCFSNVYAD SFVVKGDDV RQIAPGQTGV IADYNYKLPD DFMGCVLAWN TRNIDATSTG NYNYKYRYLR HGKLRPFERD ISNVPFSPDG K PCTPPALN CYWPLNDYGF YTTTGIGYQP YRVVVLSFEL LNAPATVCGP KLSTDLIKNQ CVNFHHHHHH UniProtKB: Spike glycoprotein |
-Macromolecule #3: ZINC ION
Macromolecule | Name: ZINC ION / type: ligand / ID: 3 / Number of copies: 1 / Formula: ZN |
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Molecular weight | Theoretical: 65.409 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: NONE |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.25 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 94460 |