+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-36345 | ||||||||||||||||||
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Title | RBD of SARS-CoV2 spike protein with ACE2 decoy | ||||||||||||||||||
Map data | |||||||||||||||||||
Sample |
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Keywords | SARS-CoV2 / spike protein / ACE2 / ACE2 decoy / VIRAL PROTEIN / VIRAL PROTEIN-PROTEIN BINDING complex | ||||||||||||||||||
Function / homology | Function and homology information positive regulation of amino acid transport / angiotensin-converting enzyme 2 / positive regulation of L-proline import across plasma membrane / Hydrolases; Acting on peptide bonds (peptidases); Metallocarboxypeptidases / angiotensin-mediated drinking behavior / regulation of systemic arterial blood pressure by renin-angiotensin / tryptophan transport / positive regulation of gap junction assembly / regulation of vasoconstriction / regulation of cardiac conduction ...positive regulation of amino acid transport / angiotensin-converting enzyme 2 / positive regulation of L-proline import across plasma membrane / Hydrolases; Acting on peptide bonds (peptidases); Metallocarboxypeptidases / angiotensin-mediated drinking behavior / regulation of systemic arterial blood pressure by renin-angiotensin / tryptophan transport / positive regulation of gap junction assembly / regulation of vasoconstriction / regulation of cardiac conduction / peptidyl-dipeptidase activity / maternal process involved in female pregnancy / angiotensin maturation / Metabolism of Angiotensinogen to Angiotensins / metallocarboxypeptidase activity / carboxypeptidase activity / negative regulation of signaling receptor activity / Attachment and Entry / positive regulation of cardiac muscle contraction / regulation of cytokine production / viral life cycle / blood vessel diameter maintenance / brush border membrane / regulation of transmembrane transporter activity / negative regulation of smooth muscle cell proliferation / negative regulation of ERK1 and ERK2 cascade / cilium / metallopeptidase activity / endocytic vesicle membrane / positive regulation of reactive oxygen species metabolic process / virus receptor activity / regulation of cell population proliferation / regulation of inflammatory response / Maturation of spike protein / endopeptidase activity / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Potential therapeutics for SARS / 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 / membrane fusion / Attachment and Entry / 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 / membrane raft / apical plasma membrane / endoplasmic reticulum lumen / 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 / extracellular space / zinc ion binding / extracellular exosome / extracellular region / identical protein binding / membrane / plasma membrane Similarity search - Function | ||||||||||||||||||
Biological species | Homo sapiens (human) / Severe acute respiratory syndrome coronavirus 2 / synthetic construct (others) | ||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.4 Å | ||||||||||||||||||
Authors | Kishikawa J / Hirose M / Kato T / Okamoto T | ||||||||||||||||||
Funding support | Japan, 5 items
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Citation | Journal: Sci Transl Med / Year: 2023 Title: An inhaled ACE2 decoy confers protection against SARS-CoV-2 infection in preclinical models. Authors: Emiko Urano / Yumi Itoh / Tatsuya Suzuki / Takanori Sasaki / Jun-Ichi Kishikawa / Kanako Akamatsu / Yusuke Higuchi / Yusuke Sakai / Tomotaka Okamura / Shuya Mitoma / Fuminori Sugihara / ...Authors: Emiko Urano / Yumi Itoh / Tatsuya Suzuki / Takanori Sasaki / Jun-Ichi Kishikawa / Kanako Akamatsu / Yusuke Higuchi / Yusuke Sakai / Tomotaka Okamura / Shuya Mitoma / Fuminori Sugihara / Akira Takada / Mari Kimura / Shuto Nakao / Mika Hirose / Tadahiro Sasaki / Ritsuko Koketsu / Shunya Tsuji / Shota Yanagida / Tatsuo Shioda / Eiji Hara / Satoaki Matoba / Yoshiharu Matsuura / Yasunari Kanda / Hisashi Arase / Masato Okada / Junichi Takagi / Takayuki Kato / Atsushi Hoshino / Yasuhiro Yasutomi / Akatsuki Saito / Toru Okamoto / Abstract: The Omicron variant continuously evolves under the humoral immune pressure exerted by vaccination and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the resulting Omicron ...The Omicron variant continuously evolves under the humoral immune pressure exerted by vaccination and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the resulting Omicron subvariants display further immune evasion and antibody escape. An engineered angiotensin-converting enzyme 2 (ACE2) decoy composed of high-affinity ACE2 and an IgG1 Fc domain could offer an alternative modality to neutralize SARS-CoV-2. We previously reported its broad spectrum and therapeutic potential in rodent models. Here, we demonstrate that the engineered ACE2 decoy retains neutralization activity against Omicron subvariants, including the currently emerging XBB and BQ.1 strains, which completely evade antibodies currently in clinical use. SARS-CoV-2, under the suboptimal concentration of neutralizing drugs, generated SARS-CoV-2 mutants escaping wild-type ACE2 decoy and monoclonal antibodies, whereas no escape mutant emerged against the engineered ACE2 decoy. Furthermore, inhalation of aerosolized decoys improved the outcomes of rodents infected with SARS-CoV-2 at a 20-fold lower dose than that of intravenous administration. Last, the engineered ACE2 decoy exhibited therapeutic efficacy for cynomolgus macaques infected with SARS-CoV-2. These results indicate that this engineered ACE2 decoy represents a promising therapeutic strategy to overcome immune-evading SARS-CoV-2 variants and that liquid aerosol inhalation could be considered as a noninvasive approach to enhance the efficacy of COVID-19 treatments. | ||||||||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_36345.map.gz | 97.3 MB | EMDB map data format | |
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Header (meta data) | emd-36345-v30.xml emd-36345.xml | 24.4 KB 24.4 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_36345_fsc.xml | 9.9 KB | Display | FSC data file |
Images | emd_36345.png | 82.6 KB | ||
Masks | emd_36345_msk_1.map | 103 MB | Mask map | |
Filedesc metadata | emd-36345.cif.gz | 8.2 KB | ||
Others | emd_36345_half_map_1.map.gz emd_36345_half_map_2.map.gz | 95.5 MB 95.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-36345 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36345 | HTTPS FTP |
-Validation report
Summary document | emd_36345_validation.pdf.gz | 1.1 MB | Display | EMDB validaton report |
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Full document | emd_36345_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | emd_36345_validation.xml.gz | 18.3 KB | Display | |
Data in CIF | emd_36345_validation.cif.gz | 23.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36345 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36345 | HTTPS FTP |
-Related structure data
Related structure data | 8jjeMC 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_36345.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.173 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_36345_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_36345_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_36345_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : RBD of SARS-CoV2 spike protein with ACE2 decoy.
Entire | Name: RBD of SARS-CoV2 spike protein with ACE2 decoy. |
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Components |
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-Supramolecule #1: RBD of SARS-CoV2 spike protein with ACE2 decoy.
Supramolecule | Name: RBD of SARS-CoV2 spike protein with ACE2 decoy. / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Molecular weight | Theoretical: 460 KDa |
-Supramolecule #2: ACE2
Supramolecule | Name: ACE2 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
-Supramolecule #3: SARS-CoV2 spike protein
Supramolecule | Name: SARS-CoV2 spike protein / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2 |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
-Macromolecule #1: Angiotensin-converting enzyme 2
Macromolecule | Name: Angiotensin-converting enzyme 2 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: angiotensin-converting enzyme 2 |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 73.198133 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MSSSSWLLLS LVAVTAAQST IEEQVKTFLD NFNHKAEDLF YQSSLASWNY NTNITEENVQ NMNNAGDKWS AFLKEQSTLA QMYPLQEIQ NLQVKLQLQA LQQNGSSVLS EDKSKRLNTI LNTMSTIYCT GKVCNPDNPQ ECLLLEPGLN EIMANSLDYN E RLWAWESW ...String: MSSSSWLLLS LVAVTAAQST IEEQVKTFLD NFNHKAEDLF YQSSLASWNY NTNITEENVQ NMNNAGDKWS AFLKEQSTLA QMYPLQEIQ NLQVKLQLQA LQQNGSSVLS EDKSKRLNTI LNTMSTIYCT GKVCNPDNPQ ECLLLEPGLN EIMANSLDYN E RLWAWESW RSEVGKQLRP LYEEYVVLKN EMARANHYED YGDYWRGDYE VNGVDGYDYS RGQLIEDVEH TFEEIKPLYE HL HAYVRAK LMNAYPSYIS PIGCLPAHLL GDMWGRFWTN LYSLTVPFGQ KPNIDVTDAM VDQAWDAQRI FKEAEKFFVS VGL PNMTQG FWENSMLTDP GNVQKACCHP TAWDLGKGDF RILMCTKVTM DDFLTAHHEM GHIQYDMAYA AQPFLLRNGA NEGF HEAVG EIMSLSAATP KHLKSIGLLS PDFQEDNETE INFLLKQALT IVGTLPFTYM LEKWRWMVFK GEIPKDQWMK KWWEM KREI VGVVEPVPHD ETYCDPASLF HVSNDYSFIR YYTRTLYQFQ FQEALCQAAK HEGPLHKCDI SNSTEAGQKL FNMLRL GKS EPWTLALENV VGAKNMNVRP LLNYFEPLFT WLKDQNKNSF VGWSTDWSPY ADEFSGGGGS GGGGSGGGGS HHHHHH UniProtKB: Angiotensin-converting enzyme 2 |
-Macromolecule #2: Spike glycoprotein
Macromolecule | Name: Spike glycoprotein / type: protein_or_peptide / ID: 2 Details: 1-2 is the signal sequence. 1216-1242 is the Trimeric Foldon to from trimeric spike. 1201-1215 and 1243 are the linkers. 1244- is the purification tag. Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: synthetic construct (others) |
Molecular weight | Theoretical: 138.621188 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: LEQCVNLTTR TQLPPAYTNS FTRGVYYPDK VFRSSVLHST QDLFLPFFSN VTWFHAIHVS GTNGTKRFDN PVLPFNDGVY FASTEKSNI IRGWIFGTTL DSKTQSLLIV NNATNVVIKV CEFQFCNDPF LGVYYHKNNK SWMESEFRVY SSANNCTFEY V SQPFLMDL ...String: LEQCVNLTTR TQLPPAYTNS FTRGVYYPDK VFRSSVLHST QDLFLPFFSN VTWFHAIHVS GTNGTKRFDN PVLPFNDGVY FASTEKSNI IRGWIFGTTL DSKTQSLLIV NNATNVVIKV CEFQFCNDPF LGVYYHKNNK SWMESEFRVY SSANNCTFEY V SQPFLMDL EGKQGNFKNL REFVFKNIDG YFKIYSKHTP INLVRDLPQG FSALEPLVDL PIGINITRFQ TLLALHRSYL TP GDSSSGW TAGAAAYYVG YLQPRTFLLK YNENGTITDA VDCALDPLSE TKCTLKSFTV EKGIYQTSNF RVQPTESIVR FPN ITNLCP FGEVFNATRF ASVYAWNRKR ISNCVADYSV LYNSASFSTF KCYGVSPTKL NDLCFTNVYA DSFVIRGDEV RQIA PGQTG KIADYNYKLP DDFTGCVIAW NSNNLDSKVG GNYNYLYRLF RKSNLKPFER DISTEIYQAG STPCNGVEGF NCYFP LQSY GFQPTNGVGY QPYRVVVLSF ELLHAPATVC GPKKSTNLVK NKCVNFNFNG LTGTGVLTES NKKFLPFQQF GRDIAD TTD AVRDPQTLEI LDITPCSFGG VSVITPGTNT SNQVAVLYQD VNCTEVPVAI HADQLTPTWR VYSTGSNVFQ TRAGCLI GA EHVNNSYECD IPIGAGICAS YQTQTNSPGS AGSVASQSII AYTMSLGAEN SVAYSNNSIA IPTNFTISVT TEILPVSM T KTSVDCTMYI CGDSTECSNL LLQYGSFCTQ LNRALTGIAV EQDKNTQEVF AQVKQIYKTP PIKDFGGFNF SQILPDPSK PSKRSFIEDL LFNKVTLADA GFIKQYGDCL GDIAARDLIC AQKFNGLTVL PPLLTDEMIA QYTSALLAGT ITSGWTFGAG AALQIPFAM QMAYRFNGIG VTQNVLYENQ KLIANQFNSA IGKIQDSLSS TASALGKLQD VVNQNAQALN TLVKQLSSNF G AISSVLND ILSRLDPPEA EVQIDRLITG RLQSLQTYVT QQLIRAAEIR ASANLAATKM SECVLGQSKR VDFCGKGYHL MS FPQSAPH GVVFLHVTYV PAQEKNFTTA PAICHDGKAH FPREGVFVSN GTHWFVTQRN FYEPQIITTD NTFVSGNCDV VIG IVNNTV YDPLQPELDS FKEELDKYFK NHTSPDVDLG DISGINASVV NIQKEIDRLN EVAKNLNESL IDLQELGKYE QYIK GSGRE NLYFQGGGGS GYIPEAPRDG QAYVRKDGEW VLLSTFLGHH HHHHHH UniProtKB: Spike glycoprotein |
-Macromolecule #7: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 7 / Number of copies: 1 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Macromolecule #8: ZINC ION
Macromolecule | Name: ZINC ION / type: ligand / ID: 8 / Number of copies: 1 / Formula: ZN |
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Molecular weight | Theoretical: 65.409 Da |
-Macromolecule #9: SULFATE ION
Macromolecule | Name: SULFATE ION / type: ligand / ID: 9 / Number of copies: 1 / Formula: SO4 |
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Molecular weight | Theoretical: 96.063 Da |
Chemical component information | ChemComp-SO4: |
-Macromolecule #10: water
Macromolecule | Name: water / type: ligand / ID: 10 / Number of copies: 1 / Formula: HOH |
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Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ChemComp-HOH: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 Component:
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Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Number grids imaged: 1 / Number real images: 7947 / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 0.085 mm / Nominal defocus max: 1.8 µm / Nominal defocus min: 0.8 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |