+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-15590 | |||||||||
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Title | BA.1 SARS-CoV-2 Spike bound to mouse ACE2 (local) | |||||||||
Map data | b1 | |||||||||
Sample |
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Function / homology | Function and homology information Metabolism of Angiotensinogen to Angiotensins / positive regulation of B cell activation / early endosome to late endosome transport / humoral immune response mediated by circulating immunoglobulin / phagocytosis, recognition / positive regulation of type IIa hypersensitivity / regulation of proteolysis / positive regulation of type I hypersensitivity / antibody-dependent cellular cytotoxicity / Fc-gamma receptor I complex binding ...Metabolism of Angiotensinogen to Angiotensins / positive regulation of B cell activation / early endosome to late endosome transport / humoral immune response mediated by circulating immunoglobulin / phagocytosis, recognition / positive regulation of type IIa hypersensitivity / regulation of proteolysis / positive regulation of type I hypersensitivity / antibody-dependent cellular cytotoxicity / Fc-gamma receptor I complex binding / phagocytosis, engulfment / endosome to lysosome transport / positive regulation of endocytosis / immunoglobulin complex, circulating / IgG immunoglobulin complex / positive regulation of amino acid transport / immunoglobulin receptor binding / 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 systemic arterial blood pressure by renin-angiotensin / immunoglobulin mediated immune response / regulation of cardiac conduction / peptidyl-dipeptidase activity / antigen processing and presentation / maternal process involved in female pregnancy / metallocarboxypeptidase activity / positive regulation of phagocytosis / complement activation, classical pathway / carboxypeptidase activity / positive regulation of cardiac muscle contraction / antigen binding / multivesicular body / virion component / negative regulation of smooth muscle cell proliferation / brush border membrane / response to bacterium / cilium / negative regulation of ERK1 and ERK2 cascade / metallopeptidase activity / positive regulation of immune response / virus receptor activity / antibacterial humoral response / Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / endopeptidase activity / 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 / symbiont entry into host cell / 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 / 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 / extracellular region / membrane / identical protein binding / metal ion binding / plasma membrane / cytosol / 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: 3.22 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_15590.map.gz | 154.6 MB | EMDB map data format | |
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Header (meta data) | emd-15590-v30.xml emd-15590.xml | 19.2 KB 19.2 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_15590_fsc.xml | 11.6 KB | Display | FSC data file |
Images | emd_15590.png | 67.2 KB | ||
Others | emd_15590_half_map_1.map.gz emd_15590_half_map_2.map.gz | 151.7 MB 151.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-15590 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-15590 | HTTPS FTP |
-Related structure data
Related structure data | 8aquMC 8aqsC 8aqtC 8aqvC 8aqwC 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_15590.map.gz / Format: CCP4 / Size: 163.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | b1 | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.0371 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: b1
File | emd_15590_half_map_1.map | ||||||||||||
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Annotation | b1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: b1
File | emd_15590_half_map_2.map | ||||||||||||
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Annotation | b1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : SARS-COV2 BA1 bound to mouse ACE2
Entire | Name: SARS-COV2 BA1 bound to mouse ACE2 |
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Components |
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-Supramolecule #1: SARS-COV2 BA1 bound to mouse ACE2
Supramolecule | Name: SARS-COV2 BA1 bound to mouse ACE2 / 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.1 spike protein
Supramolecule | Name: SARS-CoV-2 BA.1 spike protein / type: complex / ID: 2 / Chimera: Yes / Parent: 1 / Macromolecule list: #2 |
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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: #1 |
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Source (natural) | Organism: Mus musculus (house mouse) |
-Macromolecule #1: Processed angiotensin-converting enzyme 2,Ig gamma-2A chain C reg...
Macromolecule | Name: Processed angiotensin-converting enzyme 2,Ig gamma-2A chain C region, membrane-bound form type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 101.892125 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 TEWSPYADTG LEVLFQG PM DEPRGPTIKP CPPCKCPAPN LLGGPSVFIF PPKIKDVLMI SLSPIVTCVV VDVSEDDPDV QISWFVNNVE VHTAQTQT H REDYNSTLRV VSALPIQHQD WMSGKEFKCK VNNKDLPAPI ERTISKPKGS VRAPQVYVLP PPEEEMTKKQ VTLTCMVTD FMPEDIYVEW TNNGKTELNY KNTEPVLDSD GSYFMYSKLR VEKKNWVERN SYSCSVVHEG LHNHHTTKSF SRTPGKHHHH HHHHHH |
-Macromolecule #2: Spike glycoprotein,Fibritin
Macromolecule | Name: Spike glycoprotein,Fibritin / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Enterobacteria phage T4 (virus) |
Molecular weight | Theoretical: 142.558094 KDa |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
Sequence | String: MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHVISG TNGTKRFDNP VLPFNDGVY FASIEKSNII RGWIFGTTLD SKTQSLLIVN NATNVVIKVC EFQFCNDPFL DHKNNKSWME SEFRVYSSAN N CTFEYVSQ ...String: MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHVISG TNGTKRFDNP VLPFNDGVY FASIEKSNII RGWIFGTTLD SKTQSLLIVN NATNVVIKVC EFQFCNDPFL DHKNNKSWME SEFRVYSSAN N CTFEYVSQ PFLMDLEGKQ GNFKNLREFV FKNIDGYFKI YSKHTPIIVR EPEDLPQGFS ALEPLVDLPI GINITRFQTL LA LHRSYLT PGDSSSGWTA GAAAYYVGYL QPRTFLLKYN ENGTITDAVD CALDPLSETK CTLKSFTVEK GIYQTSNFRV QPT ESIVRF PNITNLCPFD EVFNATRFAS VYAWNRKRIS NCVADYSVLY NLAPFFTFKC YGVSPTKLND LCFTNVYADS FVIR GDEVR QIAPGQTGNI ADYNYKLPDD FTGCVIAWNS NKLDSKVSGN YNYLYRLFRK SNLKPFERDI STEIYQAGNK PCNGV AGFN CYFPLRSYSF RPTYGVGHQP YRVVVLSFEL LHAPATVCGP KKSTNLVKNK CVNFNFNGLK GTGVLTESNK KFLPFQ QFG RDIADTTDAV RDPQTLEILD ITPCSFGGVS VITPGTNTSN QVAVLYQGVN CTEVPVAIHA DQLTPTWRVY STGSNVF QT RAGCLIGAEY VNNSYECDIP IGAGICASYQ TQTKSHGSAS SVASQSIIAY TMSLGAENSV AYSNNSIAIP TNFTISVT T EILPVSMTKT SVDCTMYICG DSTECSNLLL QYGSFCTQLK RALTGIAVEQ DKNTQEVFAQ VKQIYKTPPI KYFGGFNFS QILPDPSKPS KRSFIEDLLF NKVTLADAGF IKQYGDCLGD IAARDLICAQ KFKGLTVLPP LLTDEMIAQY TSALLAGTIT SGWTFGAGA ALQIPFAMQM AYRFNGIGVT QNVLYENQKL IANQFNSAIG KIQDSLSSTA SALGKLQDVV NHNAQALNTL V KQLSSKFG AISSVLNDIF SRLDPPEAEV QIDRLITGRL QSLQTYVTQQ LIRAAEIRAS ANLAATKMSE CVLGQSKRVD FC GKGYHLM SFPQSAPHGV VFLHVTYVPA QEKNFTTAPA ICHDGKAHFP REGVFVSNGT HWFVTQRNFY EPQIITTDNT FVS GNCDVV IGIVNNTVYD PLQPELDSFK EELDKYFKNH TSPDVDLGDI SGINASVVNI QKEIDRLNEV AKNLNESLID LQEL GKYEQ GSGYIPEAPR DGQAYVRKDG EWVLLSTFLG RSLEVLFQGP GHHHHHHHHS AWSHPQFEKG GGSGGGGSGG SAWSH PQFE K |
-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.1 SARS-CoV-2 Spike bound to mouse ACE2 |
-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: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.8000000000000003 µm / Nominal defocus min: 0.8 µm |
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 58.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |