+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-15592 | |||||||||
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Title | BA.4/5 SARS-CoV-2 Spike bound to mouse ACE2 (local) | |||||||||
Map data | b4m | |||||||||
Sample |
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Function / homology | Function and homology information Metabolism of Angiotensinogen to Angiotensins / angiotensin-converting enzyme 2 / positive regulation of L-proline import across plasma membrane / Hydrolases; Acting on peptide bonds (peptidases); Metallocarboxypeptidases / angiotensin-mediated drinking behavior / tryptophan transport / positive regulation of gap junction assembly / regulation of cardiac conduction / peptidyl-dipeptidase activity / maternal process involved in female pregnancy ...Metabolism of Angiotensinogen to Angiotensins / angiotensin-converting enzyme 2 / positive regulation of L-proline import across plasma membrane / Hydrolases; Acting on peptide bonds (peptidases); Metallocarboxypeptidases / angiotensin-mediated drinking behavior / tryptophan transport / positive regulation of gap junction assembly / regulation of cardiac conduction / peptidyl-dipeptidase activity / maternal process involved in female pregnancy / immunoglobulin complex, circulating / immunoglobulin receptor binding / carboxypeptidase activity / positive regulation of cardiac muscle contraction / complement activation, classical pathway / negative regulation of smooth muscle cell proliferation / antigen binding / brush border membrane / cilium / negative regulation of ERK1 and ERK2 cascade / virion component / metallopeptidase activity / virus receptor activity / antibacterial humoral response / 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 / Mus musculus (house mouse) / Enterobacteria phage T4 (virus) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||
Authors | Lau K / Ni D / Beckert B / Nazarov S / Myasnikov A / Pojer F / Stahlberg H / Uchikawa E | |||||||||
Funding support | Switzerland, 1 items
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Citation | Journal: PLoS Pathog / Year: 2023 Title: Cryo-EM structures and binding of mouse and human ACE2 to SARS-CoV-2 variants of concern indicate that mutations enabling immune escape could expand host range. Authors: Dongchun Ni / Priscilla Turelli / Bertrand Beckert / Sergey Nazarov / Emiko Uchikawa / Alexander Myasnikov / Florence Pojer / Didier Trono / Henning Stahlberg / Kelvin Lau / Abstract: Investigation of potential hosts of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is crucial to understanding future risks of spillover and spillback. SARS-CoV-2 has been reported ...Investigation of potential hosts of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is crucial to understanding future risks of spillover and spillback. SARS-CoV-2 has been reported to be transmitted from humans to various animals after requiring relatively few mutations. There is significant interest in describing how the virus interacts with mice as they are well adapted to human environments, are used widely as infection models and can be infected. Structural and binding data of the mouse ACE2 receptor with the Spike protein of newly identified SARS-CoV-2 variants are needed to better understand the impact of immune system evading mutations present in variants of concern (VOC). Previous studies have developed mouse-adapted variants and identified residues critical for binding to heterologous ACE2 receptors. Here we report the cryo-EM structures of mouse ACE2 bound to trimeric Spike ectodomains of four different VOC: Beta, Omicron BA.1, Omicron BA.2.12.1 and Omicron BA.4/5. These variants represent the oldest to the newest variants known to bind the mouse ACE2 receptor. Our high-resolution structural data complemented with bio-layer interferometry (BLI) binding assays reveal a requirement for a combination of mutations in the Spike protein that enable binding to the mouse ACE2 receptor. #1: Journal: Biorxiv / Year: 2023 Title: Cryo-EM structures and binding of mouse and human ACE2 to SARS-CoV-2 variants of concern indicate that mutations enabling immune escape could expand host range Authors: Ni D / Turelli P / Beckert B / Nazarov S / Uchikawa E / Myasnikov A / Pojer F / Trono D / Stahlberg H / Lau K | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_15592.map.gz | 168.2 MB | EMDB map data format | |
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Header (meta data) | emd-15592-v30.xml emd-15592.xml | 19.2 KB 19.2 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_15592_fsc.xml | 11.9 KB | Display | FSC data file |
Images | emd_15592.png | 89.4 KB | ||
Others | emd_15592_half_map_1.map.gz emd_15592_half_map_2.map.gz | 165.4 MB 165.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-15592 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-15592 | HTTPS FTP |
-Validation report
Summary document | emd_15592_validation.pdf.gz | 1.2 MB | Display | EMDB validaton report |
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Full document | emd_15592_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | emd_15592_validation.xml.gz | 20.5 KB | Display | |
Data in CIF | emd_15592_validation.cif.gz | 26.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-15592 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-15592 | HTTPS FTP |
-Related structure data
Related structure data | 8aqwMC 8aqsC 8aqtC 8aquC 8aqvC 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_15592.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | b4m | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.0144 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: b4m
File | emd_15592_half_map_1.map | ||||||||||||
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Annotation | b4m | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: b4m
File | emd_15592_half_map_2.map | ||||||||||||
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Annotation | b4m | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : BA.4/5 SARS-CoV-2 Spike bound to mouse ACE2 (local)
Entire | Name: BA.4/5 SARS-CoV-2 Spike bound to mouse ACE2 (local) |
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Components |
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-Supramolecule #1: BA.4/5 SARS-CoV-2 Spike bound to mouse ACE2 (local)
Supramolecule | Name: BA.4/5 SARS-CoV-2 Spike bound to mouse ACE2 (local) / type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: #1-#2 |
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Molecular weight | Theoretical: 430 KDa |
-Supramolecule #2: SARS-CoV-2 BA.4/5 spike protein
Supramolecule | Name: SARS-CoV-2 BA.4/5 spike protein / type: complex / ID: 2 / Chimera: Yes / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
-Supramolecule #3: Mouse ACE2
Supramolecule | Name: Mouse ACE2 / type: complex / ID: 3 / Chimera: Yes / Parent: 1 / Macromolecule list: #2 |
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Source (natural) | Organism: Mus musculus (house mouse) |
-Macromolecule #1: Spike glycoprotein,Fibritin
Macromolecule | Name: Spike glycoprotein,Fibritin / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Enterobacteria phage T4 (virus) |
Molecular weight | Theoretical: 142.143391 KDa |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
Sequence | String: MFVFLVLLPL VSSQCVNLIT RTQSYTNSFT RGVYYPDKVF RSSVLHSTQD LFLPFFSNVT WFHAISGTNG TKRFDNPVLP FNDGVYFAS TEKSNIIRGW IFGTTLDSKT QSLLIVNNAT NVVIKVCEFQ FCNDPFLDVY YHKNNKSWME SEFRVYSSAN N CTFEYVSQ ...String: MFVFLVLLPL VSSQCVNLIT RTQSYTNSFT RGVYYPDKVF RSSVLHSTQD LFLPFFSNVT WFHAISGTNG TKRFDNPVLP FNDGVYFAS TEKSNIIRGW IFGTTLDSKT QSLLIVNNAT NVVIKVCEFQ FCNDPFLDVY YHKNNKSWME SEFRVYSSAN N CTFEYVSQ PFLMDLEGKQ GNFKNLREFV FKNIDGYFKI YSKHTPINLG RDLPQGFSAL EPLVDLPIGI NITRFQTLLA LH RSYLTPG DSSSGWTAGA AAYYVGYLQP RTFLLKYNEN GTITDAVDCA LDPLSETKCT LKSFTVEKGI YQTSNFRVQP TES IVRFPN ITNLCPFDEV FNATRFASVY AWNRKRISNC VADYSVLYNF APFFAFKCYG VSPTKLNDLC FTNVYADSFV IRGN EVSQI APGQTGNIAD YNYKLPDDFT GCVIAWNSNK LDSKVGGNYN YRYRLFRKSN LKPFERDIST EIYQAGNKPC NGVAG VNCY FPLQSYGFRP TYGVGHQPYR VVVLSFELLH APATVCGPKK STNLVKNKCV NFNFNGLTGT GVLTESNKKF LPFQQF GRD IADTTDAVRD PQTLEILDIT PCSFGGVSVI TPGTNTSNQV AVLYQGVNCT EVPVAIHADQ LTPTWRVYST GSNVFQT RA GCLIGAEYVN NSYECDIPIG AGICASYQTQ TKSHGSASSV ASQSIIAYTM SLGAENSVAY SNNSIAIPTN FTISVTTE I LPVSMTKTSV DCTMYICGDS TECSNLLLQY GSFCTQLKRA LTGIAVEQDK NTQEVFAQVK QIYKTPPIKY FGGFNFSQI LPDPSKPSKR SFIEDLLFNK VTLADAGFIK QYGDCLGDIA ARDLICAQKF NGLTVLPPLL TDEMIAQYTS ALLAGTITSG WTFGAGAAL QIPFAMQMAY RFNGIGVTQN VLYENQKLIA NQFNSAIGKI QDSLSSTASA LGKLQDVVNH NAQALNTLVK Q LSSKFGAI SSVLNDILSR LDPPEAEVQI DRLITGRLQS LQTYVTQQLI RAAEIRASAN LAATKMSECV LGQSKRVDFC GK GYHLMSF PQSAPHGVVF LHVTYVPAQE KNFTTAPAIC HDGKAHFPRE GVFVSNGTHW FVTQRNFYEP QIITTDNTFV SGN CDVVIG IVNNTVYDPL QPELDSFKEE LDKYFKNHTS PDVDLGDISG INASVVNIQK EIDRLNEVAK NLNESLIDLQ ELGK YEQGS GYIPEAPRDG QAYVRKDGEW VLLSTFLGRS LEVLFQGPGH HHHHHHHSAW SHPQFEKGGG SGGGGSGGSA WSHPQ FEK |
-Macromolecule #2: Processed angiotensin-converting enzyme 2,Ig gamma-2A chain C reg...
Macromolecule | Name: Processed angiotensin-converting enzyme 2,Ig gamma-2A chain C region, A allele type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 101.733969 KDa |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
Sequence | String: MGTLSAPPCT QRIKWKGLLL TASLLNFWNL PTTASLTEEN AKTFLNNFNQ EAEDLSYQSS LASWNYNTNI TEENAQKMSE AAAKWSAFY EEQSKTAQSF SLQEIQTPII KRQLQALQQS GSSALSADKN KQLNTILNTM STIYSTGKVC NPKNPQECLL L EPGLDEIM ...String: MGTLSAPPCT QRIKWKGLLL TASLLNFWNL PTTASLTEEN AKTFLNNFNQ EAEDLSYQSS LASWNYNTNI TEENAQKMSE AAAKWSAFY EEQSKTAQSF SLQEIQTPII KRQLQALQQS GSSALSADKN KQLNTILNTM STIYSTGKVC NPKNPQECLL L EPGLDEIM ATSTDYNSRL WAWEGWRAEV GKQLRPLYEE YVVLKNEMAR ANNYNDYGDY WRGDYEAEGA DGYNYNRNQL IE DVERTFA EIKPLYEHLH AYVRRKLMDT YPSYISPTGC LPAHLLGDMW GRFWTNLYPL TVPFAQKPNI DVTDAMMNQG WDA ERIFQE AEKFFVSVGL PHMTQGFWAN SMLTEPADGR KVVCHPTAWD LGHGDFRIKM CTKVTMDNFL TAHHEMGHIQ YDMA YARQP FLLRNGANEG FHEAVGEIMS LSAATPKHLK SIGLLPSDFQ EDSETEINFL LKQALTIVGT LPFTYMLEKW RWMVF RGEI PKEQWMKKWW EMKREIVGVV EPLPHDETYC DPASLFHVSN DYSFIRYYTR TIYQFQFQEA LCQAAKYNGS LHKCDI SNS TEAGQKLLKM LSLGNSEPWT KALENVVGAR NMDVKPLLNY FQPLFDWLKE QNRNSFVGWN TEWSPYADLE VLFQGPM DE PRGPTIKPCP PCKCPAPNLL GGPSVFIFPP KIKDVLMISL SPIVTCVVVD VSEDDPDVQI SWFVNNVEVH TAQTQTHR E DYNSTLRVVS ALPIQHQDWM SGKEFKCKVN NKDLPAPIER TISKPKGSVR APQVYVLPPP EEEMTKKQVT LTCMVTDFM PEDIYVEWTN NGKTELNYKN TEPVLDSDGS YFMYSKLRVE KKNWVERNSY SCSVVHEGLH NHHTTKSFSR TPGKHHHHHH HHHH |
-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: 7.5 |
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Vitrification | Cryogen name: ETHANE |
Details | BA.4/5 SARS-CoV-2 Spike bound to mouse ACE2 |
-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: 58.0 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: 2.8000000000000003 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |