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Yorodumi- EMDB-37702: Cryo-EM structure of SARS-CoV-2 Omicron BA.4/5 RBD in complex wit... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-37702 | |||||||||
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Title | Cryo-EM structure of SARS-CoV-2 Omicron BA.4/5 RBD in complex with rabbit ACE2 (local refinement) | |||||||||
Map data | Sharp map of SARS-CoV-2 Omicron BA.4/5 spike protein in complex with rabbit ACE2 | |||||||||
Sample |
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Keywords | Severe acute respiratory syndrome coronavirus 2 / Angiotensin-converting enzyme 2 / Spike protein / VIRAL PROTEIN | |||||||||
Function / homology | Function and homology information 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 / carboxypeptidase activity / positive regulation of cardiac muscle contraction / brush border membrane ...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 / carboxypeptidase activity / positive regulation of cardiac muscle contraction / brush border membrane / cilium / metallopeptidase activity / virus receptor activity / 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 / 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 / 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 Similarity search - Function | |||||||||
Biological species | Severe acute respiratory syndrome coronavirus 2 / Oryctolagus cuniculus (rabbit) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.14 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_37702.map.gz | 720.5 MB | EMDB map data format | |
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Header (meta data) | emd-37702-v30.xml emd-37702.xml | 16.2 KB 16.2 KB | Display Display | EMDB header |
Images | emd_37702.png | 87.3 KB | ||
Filedesc metadata | emd-37702.cif.gz | 6 KB | ||
Others | emd_37702_half_map_1.map.gz emd_37702_half_map_2.map.gz | 764.2 MB 764.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-37702 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-37702 | HTTPS FTP |
-Related structure data
Related structure data | 8woyMC 8woxC 8wozC 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_37702.map.gz / Format: CCP4 / Size: 824 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | Sharp map of SARS-CoV-2 Omicron BA.4/5 spike protein in complex with rabbit ACE2 | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.88 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-2 Omicron BA.4/5 spike...
File | emd_37702_half_map_1.map | ||||||||||||
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Annotation | Half A map of SARS-CoV-2 Omicron BA.4/5 spike protein in complex with rabbit ACE2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half B map of SARS-CoV-2 Omicron BA.4/5 spike...
File | emd_37702_half_map_2.map | ||||||||||||
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Annotation | Half B map of SARS-CoV-2 Omicron BA.4/5 spike protein in complex with rabbit ACE2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Cryo-EM structure of SARS-CoV-2 Omicron BA.4/5 RBD in complex wit...
Entire | Name: Cryo-EM structure of SARS-CoV-2 Omicron BA.4/5 RBD in complex with rabbit ACE2 (local refinement) |
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Components |
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-Supramolecule #1: Cryo-EM structure of SARS-CoV-2 Omicron BA.4/5 RBD in complex wit...
Supramolecule | Name: Cryo-EM structure of SARS-CoV-2 Omicron BA.4/5 RBD in complex with rabbit ACE2 (local refinement) type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
-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: 69.017414 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
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 PYA 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 2 |
Molecular weight | Theoretical: 26.084525 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: RVQPTESIVR FPNITNLCPF DEVFNATRFA SVYAWNRKRI SNCVADYSVL YNFAPFFAFK CYGVSPTKLN DLCFTNVYAD SFVIRGNEV SQIAPGQTGN IADYNYKLPD DFTGCVIAWN SNKLDSKVGG NYNYRYRLFR KSNLKPFERD ISTEIYQAGN K PCNGVAGV ...String: 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 |
-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 |
-Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 1 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-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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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: NONE |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.14 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 317529 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |