+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-41786 | |||||||||
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Title | PRD-0038 RBD bound to R. alcyone ACE2 | |||||||||
Map data | ||||||||||
Sample |
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Keywords | Sarbecoviruses / Spike glycoprotein / fusion protein / neutralizing antibodies / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID / inhibitor / VIRAL PROTEIN | |||||||||
Biological species | Sarbecovirus / Rhinolophus alcyone (Halcyon horseshoe bat) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||
Authors | Park YJ / Veesler D | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Cell Host Microbe / Year: 2023 Title: Broad receptor tropism and immunogenicity of a clade 3 sarbecovirus. Authors: Jimin Lee / Samantha K Zepeda / Young-Jun Park / Ashley L Taylor / Joel Quispe / Cameron Stewart / Elizabeth M Leaf / Catherine Treichel / Davide Corti / Neil P King / Tyler N Starr / David Veesler / Abstract: Although Rhinolophus bats harbor diverse clade 3 sarbecoviruses, the structural determinants of receptor tropism along with the antigenicity of their spike (S) glycoproteins remain uncharacterized. ...Although Rhinolophus bats harbor diverse clade 3 sarbecoviruses, the structural determinants of receptor tropism along with the antigenicity of their spike (S) glycoproteins remain uncharacterized. Here, we show that the African Rhinolophus bat clade 3 sarbecovirus PRD-0038 S has a broad angiotensin-converting enzyme 2 (ACE2) usage and that receptor-binding domain (RBD) mutations further expand receptor promiscuity and enable human ACE2 utilization. We determine a cryo-EM structure of the PRD-0038 RBD bound to Rhinolophus alcyone ACE2, explaining receptor tropism and highlighting differences with SARS-CoV-1 and SARS-CoV-2. Characterization of PRD-0038 S using cryo-EM and monoclonal antibody reactivity reveals its distinct antigenicity relative to SARS-CoV-2 and identifies PRD-0038 cross-neutralizing antibodies for pandemic preparedness. PRD-0038 S vaccination elicits greater titers of antibodies cross-reacting with vaccine-mismatched clade 2 and clade 1a sarbecoviruses compared with SARS-CoV-2 S due to broader antigenic targeting, motivating the inclusion of clade 3 antigens in next-generation vaccines for enhanced resilience to viral evolution. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_41786.map.gz | 118 MB | EMDB map data format | |
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Header (meta data) | emd-41786-v30.xml emd-41786.xml | 16.8 KB 16.8 KB | Display Display | EMDB header |
Images | emd_41786.png | 71.2 KB | ||
Filedesc metadata | emd-41786.cif.gz | 5.3 KB | ||
Others | emd_41786_additional_1.map.gz emd_41786_half_map_1.map.gz emd_41786_half_map_2.map.gz | 61.9 MB 115.9 MB 115.9 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-41786 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-41786 | HTTPS FTP |
-Validation report
Summary document | emd_41786_validation.pdf.gz | 733.6 KB | Display | EMDB validaton report |
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Full document | emd_41786_full_validation.pdf.gz | 733.2 KB | Display | |
Data in XML | emd_41786_validation.xml.gz | 12.4 KB | Display | |
Data in CIF | emd_41786_validation.cif.gz | 14.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-41786 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-41786 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_41786.map.gz / Format: CCP4 / Size: 125 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: 1 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: #1
File | emd_41786_additional_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_41786_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_41786_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : PRD-0038 RBD bound to R. alcyone ACE2
Entire | Name: PRD-0038 RBD bound to R. alcyone ACE2 |
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Components |
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-Supramolecule #1: PRD-0038 RBD bound to R. alcyone ACE2
Supramolecule | Name: PRD-0038 RBD bound to R. alcyone ACE2 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Sarbecovirus |
-Macromolecule #1: Rhinolophus alycone ACE2
Macromolecule | Name: Rhinolophus alycone ACE2 / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Rhinolophus alcyone (Halcyon horseshoe bat) |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MSGSSWLFLS LVAVAAAQST PEDLAKIFLD NFNSEAENLS HQSSLASWEY NTNISDENIQ KMDEAGAKWS DFYETQSKHA KNFSLEEIHN DTVKLQLQIL QQSGSPVLSE DKSKRLNSIL NAMSTIYSTG KVCRPNNPQE CLLLEPGLDN IMGTSKDYNE RLWAWEGWRA ...String: MSGSSWLFLS LVAVAAAQST PEDLAKIFLD NFNSEAENLS HQSSLASWEY NTNISDENIQ KMDEAGAKWS DFYETQSKHA KNFSLEEIHN DTVKLQLQIL QQSGSPVLSE DKSKRLNSIL NAMSTIYSTG KVCRPNNPQE CLLLEPGLDN IMGTSKDYNE RLWAWEGWRA EVGKQLRPLY EEYVVLKNEM ARGYHYEDYG DYWRRDYETE GSPDLEYSRD QLTKDVERIF AEIKPLYEQL HAYVRTKLMD TYPFHISPTG CLPAHLLGDM WGRFWTNLYP LTVPFAQKPN IDVTDAMLNQ TWDAKRIFKE AEKFFVSIGL PHMTEGFWNN SMLTDPGDGR KVVCHPTAWD LGKGDFRIKM CTKVTMEDFL TAHHEMGHIQ YDMAYASQPY LLRNGANEGF HEAVGEVMSL SVATPKHLKT MGLLSPDFLE DNETEINFLF KQALTIVGTL PFTYMLEKWR WMVFKGEIPK EEWMTKWWEM KRKIVGVVEP VPHDETYCDP ASLFHVANDY SFIRYYTRTI FEFQFHEALC RIAKHDGPLH KCDISNSTDA GKKLHQMLSV GKSQPWTSVL KDFVDSKDMD VGPLLRYFEP LYTWLKEQNR NSFVGWNTDW SPYADQSIKV RISLKSALGE KAYEWNNNEM YLFRSSVAYA MREYFLKTKN QTILFGEEDV WVSNLKPRIS FNFYVTSPRN LSDIIPRPEV EGAIRMSRSR INDAFRLDDN SLEFLGIQPT LGPPYQPPVT HHHHHHHHGG SSGLNDIFEA QKIEWHE |
-Macromolecule #2: PRD-0038 RBD
Macromolecule | Name: PRD-0038 RBD / type: protein_or_peptide / ID: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Sarbecovirus |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MGILPSPGMP ALLSLVSLLS VLLMGCVARF PNITNLCPFG QVFNASKFPS VYAWERLRIS DCVADYSVLY NSSSSFSTFK CYGVSPTKLN DLCFSSVYAD YFVVKGDDVR QIAPAQTGVI ADYNYKLPDD FTGCVLAWNT NSVDSKQGNN FYYRLFRHGK IKPYERDISN ...String: MGILPSPGMP ALLSLVSLLS VLLMGCVARF PNITNLCPFG QVFNASKFPS VYAWERLRIS DCVADYSVLY NSSSSFSTFK CYGVSPTKLN DLCFSSVYAD YFVVKGDDVR QIAPAQTGVI ADYNYKLPDD FTGCVLAWNT NSVDSKQGNN FYYRLFRHGK IKPYERDISN VLYNSAGGTC SSTSQLGCYE PLKSYGFTPT VGVGYQPYRV VVLSFELLNA PATVCGPKKS THHHHHHHHG GSSGLNDIFE AQKIEWHE |
-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: GATAN K3 (6k x 4k) / Average electron dose: 60.0 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: 2.5 µm / Nominal defocus min: 0.5 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: NONE |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 304806 |
Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |