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Yorodumi- EMDB-32379: Structure of SARS-CoV-2 spike receptor-binding domain F486L mutat... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-32379 | |||||||||
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Title | Structure of SARS-CoV-2 spike receptor-binding domain F486L mutation complexed with American mink ACE2 | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information 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 ...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 / membrane fusion / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / 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 / 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 / identical protein binding / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Severe acute respiratory syndrome coronavirus 2 | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.9 Å | |||||||||
Authors | Su C / Qi JX / Gao GF | |||||||||
Funding support | 1 items
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Citation | Journal: J Virol / Year: 2022 Title: Molecular Basis of Mink ACE2 Binding to SARS-CoV-2 and Its Mink-Derived Variants. Authors: Chao Su / Juanhua He / Pengcheng Han / Bin Bai / Dedong Li / Jian Cao / Mingxiong Tian / Yu Hu / Anqi Zheng / Sheng Niu / Qian Chen / Xiaoyu Rong / Yanfang Zhang / Weiwei Li / Jianxun Qi / ...Authors: Chao Su / Juanhua He / Pengcheng Han / Bin Bai / Dedong Li / Jian Cao / Mingxiong Tian / Yu Hu / Anqi Zheng / Sheng Niu / Qian Chen / Xiaoyu Rong / Yanfang Zhang / Weiwei Li / Jianxun Qi / Xin Zhao / Mengsu Yang / Qihui Wang / George Fu Gao / Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted between humans and minks, and some mutations in the spike (S) protein, especially in the receptor-binding domain (RBD), ...Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted between humans and minks, and some mutations in the spike (S) protein, especially in the receptor-binding domain (RBD), have been identified in mink-derived viruses. Here, we examined binding of the mink angiotensin-converting enzyme 2 (ACE2) receptor to mink-derived and important human-originating variants, and we demonstrated that most of the RBD variants increased the binding affinities to mink ACE2 (mkACE2). Cryo-electron microscopy structures of the mkACE2-RBD Y453F (with a Y-to-F change at position 453) and mkACE2-RBD F486L complexes helped identify the key residues that facilitate changes in mkACE2 binding affinity. Additionally, the data indicated that the Y453F and F486L mutations reduced the binding affinities to some human monoclonal antibodies, and human vaccinated sera efficiently prevented infection of human cells by pseudoviruses expressing Y453F, F486L, or N501T RBD. Our findings provide an important molecular mechanism for the rapid adaptation of SARS-CoV-2 in minks and highlight the potential influence of the main mink-originating variants for humans. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a broad range of hosts. Mink-derived SARS-CoV-2 can transmit back to humans. There is an urgent need to understand the binding mechanism of mink-derived SARS-CoV-2 variants to mink receptor. In this study, we identified all mutations in the receptor-binding domain (RBD) of spike (S) protein from mink-derived SARS-CoV-2, and we demonstrated the enhanced binding affinity of mink angiotensin-converting enzyme 2 (ACE2) to most of the mink-derived RBD variants as well as important human-originating RBD variants. Cryo-electron microscopy structures revealed that the Y453F and F486L mutations enhanced the binding forces in the interaction interface. In addition, Y453F and F486L mutations reduced the binding affinities to some human monoclonal antibodies, and the SARS-CoV-2 pseudoviruses with Y453F, F486L, or N501T mutations were neutralized by human vaccinated sera. Therefore, our results provide valuable information for understanding the cross-species transmission mechanism of SARS-CoV-2. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_32379.map.gz | 167.5 MB | EMDB map data format | |
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Header (meta data) | emd-32379-v30.xml emd-32379.xml | 12.8 KB 12.8 KB | Display Display | EMDB header |
Images | emd_32379.png | 37.8 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-32379 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-32379 | HTTPS FTP |
-Validation report
Summary document | emd_32379_validation.pdf.gz | 486.8 KB | Display | EMDB validaton report |
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Full document | emd_32379_full_validation.pdf.gz | 486.4 KB | Display | |
Data in XML | emd_32379_validation.xml.gz | 6.9 KB | Display | |
Data in CIF | emd_32379_validation.cif.gz | 7.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32379 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32379 | HTTPS FTP |
-Related structure data
Related structure data | 7wa1MC 7w8sC 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_32379.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.669 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Sample components
-Entire : Cryo-EM structure of SARS-CoV-2 RBD F486L complexed with American...
Entire | Name: Cryo-EM structure of SARS-CoV-2 RBD F486L complexed with American mink ACE2 |
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Components |
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-Supramolecule #1: Cryo-EM structure of SARS-CoV-2 RBD F486L complexed with American...
Supramolecule | Name: Cryo-EM structure of SARS-CoV-2 RBD F486L complexed with American mink ACE2 type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Homo sapiens (human) |
-Supramolecule #2: American mink ACE2
Supramolecule | Name: American mink ACE2 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
-Supramolecule #3: SARS-CoV-2 RBD
Supramolecule | Name: SARS-CoV-2 RBD / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2 |
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-Macromolecule #1: Angiotensin-converting enzyme 2
Macromolecule | Name: Angiotensin-converting enzyme 2 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 70.562195 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: STTEDLAKTF LEKFNYEAEE LSYQNSLASW NYNTNITDEN IQKMNIAGAK WSAFYEEESQ HAKTYPLEEI QDPIIKRQLR ALQQSGSSV LSADKRERLN TILNAMSTIY STGKACNPNN PQECLLLEPG LDDIMENSKD YNERLWAWEG WRSEVGKQLR P LYEEYVAL ...String: STTEDLAKTF LEKFNYEAEE LSYQNSLASW NYNTNITDEN IQKMNIAGAK WSAFYEEESQ HAKTYPLEEI QDPIIKRQLR ALQQSGSSV LSADKRERLN TILNAMSTIY STGKACNPNN PQECLLLEPG LDDIMENSKD YNERLWAWEG WRSEVGKQLR P LYEEYVAL KNEMARANNY EDYGDYWRGD YEEEWADGYN YSRNQLIEDV EHTFTQIKPL YEHLHAYVRA KLMDAYPSRI SP TGCLPAH LLGDMWGRFW TNLYPLMVPF GQKPNIDVTD AMVNQSWDAR RIFKEAEKFF VSVGLPNMTE GFWQNSMLTE PGD NRKVVC HPTAWDLGKH DFRIKMCTKV TMDDFLTAHH EMGHIQYDMA YAAQPFLLRN GANEGFHEAV GEIMSLSAAT PNHL KNIGL LPPDFSEDSE TDINFLLKQA LTIVGTLPFT YMLEKWRWMV FKGEIPKEQW MQKWWEMKRD IVGVVEPLPH DETYC DPAA LFHVANDYSF IRYYTRTIYQ FQFQEALCQI AKHEGPLYKC DISNSREAGQ KLHEMLSLGR SKPWTFALER VVGAKT MDV RPLLNYFEPL FTWLKEQNRN SFVGWNTDWS PYADHHHHHH |
-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: 25.917203 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: RVQPTESIVR FPNITNLCPF GEVFNATRFA SVYAWNRKRI SNCVADYSVL YNSASFSTFK CYGVSPTKLN DLCFTNVYAD SFVIRGDEV RQIAPGQTGK IADYNYKLPD DFTGCVIAWN SNNLDSKVGG NYNYLYRLFR KSNLKPFERD ISTEIYQAGS T PCNGVEGL ...String: RVQPTESIVR FPNITNLCPF GEVFNATRFA SVYAWNRKRI SNCVADYSVL YNSASFSTFK CYGVSPTKLN DLCFTNVYAD SFVIRGDEV RQIAPGQTGK IADYNYKLPD DFTGCVIAWN SNNLDSKVGG NYNYLYRLFR KSNLKPFERD ISTEIYQAGS T PCNGVEGL NCYFPLQSYG FQPTNGVGYQ PYRVVVLSFE LLHAPATVCG PKKSTNLVKN KCVNFHHHHH H |
-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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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / 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: PDB ENTRY PDB model - PDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.9 Å / Resolution method: OTHER / Number images used: 464172 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |