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- EMDB-32379: Structure of SARS-CoV-2 spike receptor-binding domain F486L mutat... -

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Basic information

Entry
Database: EMDB / ID: EMD-32379
TitleStructure of SARS-CoV-2 spike receptor-binding domain F486L mutation complexed with American mink ACE2
Map data
Sample
  • Complex: Cryo-EM structure of SARS-CoV-2 RBD F486L complexed with American mink ACE2
    • Complex: American mink ACE2
      • Protein or peptide: Angiotensin-converting enzyme 2
    • Complex: SARS-CoV-2 RBD
      • Protein or peptide: Spike protein S1
  • Ligand: ZINC ION
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 / host cell endoplasmic reticulum-Golgi intermediate compartment membrane ...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 / 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 / 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
Spike (S) protein S1 subunit, receptor-binding domain, SARS-CoV-2 / Spike (S) protein S1 subunit, N-terminal domain, SARS-CoV-like / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Spike glycoprotein, N-terminal domain superfamily / Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile. / Spike glycoprotein, betacoronavirus / Spike (S) protein S1 subunit, receptor-binding domain, betacoronavirus / Spike S1 subunit, receptor binding domain superfamily, betacoronavirus / Betacoronavirus spike glycoprotein S1, receptor binding / Spike glycoprotein S1, N-terminal domain, betacoronavirus-like ...Spike (S) protein S1 subunit, receptor-binding domain, SARS-CoV-2 / Spike (S) protein S1 subunit, N-terminal domain, SARS-CoV-like / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Spike glycoprotein, N-terminal domain superfamily / Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile. / Spike glycoprotein, betacoronavirus / Spike (S) protein S1 subunit, receptor-binding domain, betacoronavirus / Spike S1 subunit, receptor binding domain superfamily, betacoronavirus / Betacoronavirus spike glycoprotein S1, receptor binding / Spike glycoprotein S1, N-terminal domain, betacoronavirus-like / Betacoronavirus-like spike glycoprotein S1, N-terminal / Spike glycoprotein S2, coronavirus, heptad repeat 1 / Spike glycoprotein S2, coronavirus, heptad repeat 2 / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 2 (HR2) region profile. / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 1 (HR1) region profile. / Spike glycoprotein S2 superfamily, coronavirus / Spike glycoprotein S2, coronavirus / Coronavirus spike glycoprotein S2 / Coronavirus spike glycoprotein S1, C-terminal / Coronavirus spike glycoprotein S1, C-terminal
Similarity search - Domain/homology
Biological speciesHomo sapiens (human) / Severe acute respiratory syndrome coronavirus 2
Methodsingle particle reconstruction / cryo EM / Resolution: 2.9 Å
AuthorsSu C / Qi JX / Gao GF
Funding support1 items
OrganizationGrant numberCountry
Not funded
CitationJournal: 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
DepositionDec 11, 2021-
Header (metadata) releaseAug 17, 2022-
Map releaseAug 17, 2022-
UpdateApr 12, 2023-
Current statusApr 12, 2023Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

emd_32379.png

Downloads & links

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Map

FileDownload / File: emd_32379.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 0.669 Å
Density
Contour LevelBy AUTHOR: 0.25
Minimum - Maximum-2.125633 - 3.2836835
Average (Standard dev.)-9.425637e-06 (±0.06908236)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions360360360
Spacing360360360
CellA=B=C: 240.84001 Å
α=β=γ: 90.0 °

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Supplemental data

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Sample components

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Entire : Cryo-EM structure of SARS-CoV-2 RBD F486L complexed with American...

EntireName: Cryo-EM structure of SARS-CoV-2 RBD F486L complexed with American mink ACE2
Components
  • Complex: Cryo-EM structure of SARS-CoV-2 RBD F486L complexed with American mink ACE2
    • Complex: American mink ACE2
      • Protein or peptide: Angiotensin-converting enzyme 2
    • Complex: SARS-CoV-2 RBD
      • Protein or peptide: Spike protein S1
  • Ligand: ZINC ION

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Supramolecule #1: Cryo-EM structure of SARS-CoV-2 RBD F486L complexed with American...

SupramoleculeName: 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
Source (natural)Organism: Homo sapiens (human)

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Supramolecule #2: American mink ACE2

SupramoleculeName: American mink ACE2 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2

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Supramolecule #3: SARS-CoV-2 RBD

SupramoleculeName: SARS-CoV-2 RBD / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2

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Macromolecule #1: Angiotensin-converting enzyme 2

MacromoleculeName: Angiotensin-converting enzyme 2 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 70.562195 KDa
Recombinant expressionOrganism: Trichoplusia ni (cabbage looper)
SequenceString: 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

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Macromolecule #2: Spike protein S1

MacromoleculeName: Spike protein S1 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2
Molecular weightTheoretical: 25.917203 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: 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

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Macromolecule #3: ZINC ION

MacromoleculeName: ZINC ION / type: ligand / ID: 3 / Number of copies: 1 / Formula: ZN
Molecular weightTheoretical: 65.409 Da

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 8
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination 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

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Image processing

Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

6lzg

Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.9 Å / Resolution method: OTHER / Number images used: 464172
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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