+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-26378 | |||||||||
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Title | Cryo-EM structure of PDF-2180 Spike glycoprotein | |||||||||
Map data | Sharpen map | |||||||||
Sample |
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Keywords | Bat coronavirus / Coronavirus / PDF-2180 / spike glycoprotein / VIRAL PROTEIN / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID | |||||||||
Function / homology | Function and homology information endocytosis involved in viral entry into host cell / receptor-mediated virion attachment to host cell / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / host cell plasma membrane / virion membrane / membrane Similarity search - Function | |||||||||
Biological species | Bat coronavirus / PREDICT/PDF-2180 (virus) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.5 Å | |||||||||
Authors | Tortorici MA / Veesler D / Seattle Structural Genomics Center for Infectious Disease (SSGCID) | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Nature / Year: 2022 Title: Close relatives of MERS-CoV in bats use ACE2 as their functional receptors. Authors: Qing Xiong / Lei Cao / Chengbao Ma / M Alejandra Tortorici / Chen Liu / Junyu Si / Peng Liu / Mengxue Gu / Alexandra C Walls / Chunli Wang / Lulu Shi / Fei Tong / Meiling Huang / Jing Li / ...Authors: Qing Xiong / Lei Cao / Chengbao Ma / M Alejandra Tortorici / Chen Liu / Junyu Si / Peng Liu / Mengxue Gu / Alexandra C Walls / Chunli Wang / Lulu Shi / Fei Tong / Meiling Huang / Jing Li / Chufeng Zhao / Chao Shen / Yu Chen / Huabin Zhao / Ke Lan / Davide Corti / David Veesler / Xiangxi Wang / Huan Yan / Abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) and several bat coronaviruses use dipeptidyl peptidase-4 (DPP4) as an entry receptor. However, the receptor for NeoCoV-the closest known MERS- ...Middle East respiratory syndrome coronavirus (MERS-CoV) and several bat coronaviruses use dipeptidyl peptidase-4 (DPP4) as an entry receptor. However, the receptor for NeoCoV-the closest known MERS-CoV relative found in bats-remains unclear. Here, using a pseudotype virus entry assay, we found that NeoCoV and its close relative, PDF-2180, can efficiently bind to and use specific bat angiotensin-converting enzyme 2 (ACE2) orthologues and, less favourably, human ACE2 as entry receptors through their receptor-binding domains (RBDs) on the spike (S) proteins. Cryo-electron microscopy analysis revealed an RBD-ACE2 binding interface involving protein-glycan interactions, distinct from those of other known ACE2-using coronaviruses. We identified residues 337-342 of human ACE2 as a molecular determinant restricting NeoCoV entry, whereas a NeoCoV S pseudotyped virus containing a T510F RBD mutation efficiently entered cells expressing human ACE2. Although polyclonal SARS-CoV-2 antibodies or MERS-CoV RBD-specific nanobodies did not cross-neutralize NeoCoV or PDF-2180, an ACE2-specific antibody and two broadly neutralizing betacoronavirus antibodies efficiently inhibited these two pseudotyped viruses. We describe MERS-CoV-related viruses that use ACE2 as an entry receptor, underscoring a promiscuity of receptor use and a potential zoonotic threat. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_26378.map.gz | 230.2 MB | EMDB map data format | |
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Header (meta data) | emd-26378-v30.xml emd-26378.xml | 18.5 KB 18.5 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_26378_fsc.xml | 13.1 KB | Display | FSC data file |
Images | emd_26378.png | 102 KB | ||
Filedesc metadata | emd-26378.cif.gz | 6.6 KB | ||
Others | emd_26378_additional_1.map.gz emd_26378_half_map_1.map.gz emd_26378_half_map_2.map.gz | 123.4 MB 226.9 MB 226.9 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-26378 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-26378 | HTTPS FTP |
-Validation report
Summary document | emd_26378_validation.pdf.gz | 1011.6 KB | Display | EMDB validaton report |
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Full document | emd_26378_full_validation.pdf.gz | 1011.2 KB | Display | |
Data in XML | emd_26378_validation.xml.gz | 21.5 KB | Display | |
Data in CIF | emd_26378_validation.cif.gz | 27.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26378 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26378 | HTTPS FTP |
-Related structure data
Related structure data | 7u6rMC 7wpoC 7wpzC 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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-Map
File | Download / File: emd_26378.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | Sharpen map | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.05 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: Unsharpened map
File | emd_26378_additional_1.map | ||||||||||||
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Annotation | Unsharpened map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half B map
File | emd_26378_half_map_1.map | ||||||||||||
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Annotation | Half_B map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half A map
File | emd_26378_half_map_2.map | ||||||||||||
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Annotation | Half_A map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : PREDICT/PDF-2180
Entire | Name: PREDICT/PDF-2180 (virus) |
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Components |
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-Supramolecule #1: PREDICT/PDF-2180
Supramolecule | Name: PREDICT/PDF-2180 / type: virus / ID: 1 / Parent: 0 / Macromolecule list: #1 / NCBI-ID: 2042537 / Sci species name: PREDICT/PDF-2180 / Virus type: VIRION / Virus isolate: OTHER / Virus enveloped: Yes / Virus empty: Yes |
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Host (natural) | Organism: Pipistrellus cf. hesperidus |
-Macromolecule #1: PDF-2180 Spike glycoprotein
Macromolecule | Name: PDF-2180 Spike glycoprotein / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Bat coronavirus |
Molecular weight | Theoretical: 147.475578 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MTYSVSLLMC LLTFIGANAK IVSIPGGVGT GACPQVDMQP SYFIKHNWPE PIDMNKADGV IYPNGRTYSN ITLQTTNLFP RNGDLGTQY VYSASNEKSR TSNVAFISNY SYYGNPFGDG IVIRIGQNSN KTGSVIVGTA QTTIKKIYPA LMLGSSFGNF S VNNKSGAY ...String: MTYSVSLLMC LLTFIGANAK IVSIPGGVGT GACPQVDMQP SYFIKHNWPE PIDMNKADGV IYPNGRTYSN ITLQTTNLFP RNGDLGTQY VYSASNEKSR TSNVAFISNY SYYGNPFGDG IVIRIGQNSN KTGSVIVGTA QTTIKKIYPA LMLGSSFGNF S VNNKSGAY FNHTLLILPS KCGTVFQVAY CLLQPRTDSY CPGNANYVSY ALIDSPTDCT SADESKRRNG LEDIKKYFNL VN CTYFEEF NVTADERAEW FGITQDSQGV HLYTSRKNGF NSNNLFLFAS VPIYDKINYY TVIPRSIITP ANQRSAWAAF YVY PLHQLS YLLNFDVNGY ITQAADCGYN DYTQLVCSYG DFNMKSGVYS TSYYSAKPVG AYYEAHVYPD CNFTDLFREN APTI MQYKR QVFTRCNYNL TLLLSLVQVD EFVCDKITPE ALATGCYSSL TVDWFAFPYA WKSYLAIGSA DRIVRFNYNQ DYSNP SCRI HSKVNSSVGI SYSGLYSYIT NCNYGGFNKD DVVKPGGRAS QPCVTGALNS PTNGQVWSFN FGGVPYRTSR LTYTDH LKN PLDMVYVITV KYEPGAETVC PKQVRPDYST NITGLLGSCI SYDIYGITGT GVFQLCNATG IPQQKFVYDK FDNIIGF HS DDGNYYCVAP CVSVPVSVIY DDNTNQYATL FGSVACQHIS TMAAQFSRET RASLVSRNMQ NLLQTSVGCV MGFHETND T VEDCNLSLGQ SLCAIPPNTN LRVGRSTFGL GSLAYNSPLR VDALNSSEFK VSLPLNFTFG VTQEYIETSI QKITVDCKQ YVCNGFAKCE KLLEQYGQFC SKINQALHGA NLRQDDFVRN LFESVKTPQT VPLTTGFGGE FNLTLLEPLS VSTGSSNARS ALEELLFDK VTIADPGYMQ GYDDCMQQGP ASARDLICAQ YVAGYKVLPP LMDVNMEAAY TSSLLGSIAG AGWTAGLSSF A AIPFAQSI FYRLNGVGIT QQVLSENQKI IANKFNQALG AMQTGFTTTN EAFQKVQDAV NTNAQALAKL ASELSNTFGA IS SSIGDII QRLDVLEQEV QIDRLINGRL TTLNAFVAQQ LVRSESAARS AQLAKDKVNE CVKSQSTRSG FCGQGTHIVS FVI NAPNGL YFMHVGYHPS QHIEVVAAYG LCDAANPTNC IAPVNGYFIK NQTTRGVDDW SYTGSSFYAP EPITTLNTRY VAPQ VTFQN ISTNLPPPLL GNSTGTDFKD ELDEFFKNVS TSIPNFGALT QINTTLLDLS DEMLALQQVV KALNESYIDL KELGN YTYY NKGSGRENLY FQGGGGSGYI PEAPRDGQAY VRKDGEWVLL STFLGHHHHH HHH UniProtKB: Spike glycoprotein |
-Macromolecule #3: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 3 / Number of copies: 39 / 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: 8 |
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Sugar embedding | Material: Tris buffer saline |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 70.0 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: 1.5 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |