+Open data
-Basic information
Entry | Database: PDB / ID: 7u6r | ||||||
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Title | Cryo-EM structure of PDF-2180 Spike glycoprotein | ||||||
Components | PDF-2180 Spike glycoprotein | ||||||
Keywords | VIRAL PROTEIN / Bat coronavirus / Coronavirus / PDF-2180 / spike glycoprotein / 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 | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.5 Å | ||||||
Authors | Tortorici, M.A. / Veesler, D. / Seattle Structural Genomics Center for Infectious Disease (SSGCID) | ||||||
Funding support | United States, 1items
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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
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7u6r.cif.gz | 623 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7u6r.ent.gz | 496.9 KB | Display | PDB format |
PDBx/mmJSON format | 7u6r.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7u6r_validation.pdf.gz | 1.8 MB | Display | wwPDB validaton report |
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Full document | 7u6r_full_validation.pdf.gz | 1.8 MB | Display | |
Data in XML | 7u6r_validation.xml.gz | 98.5 KB | Display | |
Data in CIF | 7u6r_validation.cif.gz | 150.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/u6/7u6r ftp://data.pdbj.org/pub/pdb/validation_reports/u6/7u6r | HTTPS FTP |
-Related structure data
Related structure data | 26378MC 7wpoC 7wpzC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 147475.578 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Bat coronavirus / Cell line (production host): HEK-293 F / Production host: Homo sapiens (human) / References: UniProt: A0A1W6ASU7 #2: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #3: Sugar | ChemComp-NAG / Has ligand of interest | N | Has protein modification | Y | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: PREDICT/PDF-2180 / Type: VIRUS / Entity ID: #1 / Source: RECOMBINANT |
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Source (natural) | Organism: PREDICT/PDF-2180 (virus) |
Source (recombinant) | Organism: HEK-293 F cells |
Details of virus | Empty: YES / Enveloped: YES / Isolate: OTHER / Type: VIRION |
Natural host | Organism: Pipistrellus cf. hesperidus |
Buffer solution | pH: 8 |
Specimen | Embedding applied: YES / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
EM embedding | Material: Tris buffer saline |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1500 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 70 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 2.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 47094 / Symmetry type: POINT |