+Open data
-Basic information
Entry | Database: PDB / ID: 8aqw | ||||||
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Title | BA.4/5 SARS-CoV-2 Spike bound to mouse ACE2 (local) | ||||||
Components |
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Keywords | VIRAL PROTEIN / SARS-COV2 / omicron / Spike / RBD / mouse / ACE2 / ANTIVIRAL PROTEIN / BA4/5 | ||||||
Function / homology | Function and homology information Metabolism of Angiotensinogen to Angiotensins / Fc-gamma receptor I complex binding / IgG immunoglobulin complex / 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 cardiac conduction ...Metabolism of Angiotensinogen to Angiotensins / Fc-gamma receptor I complex binding / IgG immunoglobulin complex / 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 cardiac conduction / peptidyl-dipeptidase activity / maternal process involved in female pregnancy / immunoglobulin complex, circulating / immunoglobulin receptor binding / carboxypeptidase activity / positive regulation of cardiac muscle contraction / complement activation, classical pathway / virion component / antigen binding / brush border membrane / negative regulation of smooth muscle cell proliferation / cilium / negative regulation of ERK1 and ERK2 cascade / metallopeptidase activity / virus receptor activity / antibacterial humoral response / Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / endopeptidase activity / host cell surface / host extracellular space / 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 / apical plasma membrane / 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 / proteolysis / extracellular space / membrane / identical protein binding / metal ion binding / plasma membrane / cytoplasm Similarity search - Function | ||||||
Biological species | Severe acute respiratory syndrome coronavirus 2 Enterobacteria phage T4 (virus) Mus musculus (house mouse) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||
Authors | Lau, K. / Ni, D. / Beckert, B. / Nazarov, S. / Myasnikov, A. / Pojer, F. / Stahlberg, H. / Uchikawa, E. | ||||||
Funding support | Switzerland, 1items
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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
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8aqw.cif.gz | 189 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8aqw.ent.gz | 132.3 KB | Display | PDB format |
PDBx/mmJSON format | 8aqw.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/aq/8aqw ftp://data.pdbj.org/pub/pdb/validation_reports/aq/8aqw | HTTPS FTP |
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-Related structure data
Related structure data | 15592MC 8aqsC 8aqtC 8aquC 8aqvC 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: 142143.391 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2, (gene. exp.) Enterobacteria phage T4 (virus) Gene: S, 2, wac / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: P0DTC2, UniProt: P10104 |
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#2: Protein | Mass: 101733.969 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Gene: Ace2, Ighg / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: Q8R0I0, UniProt: P01863 |
#3: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose |
#4: Sugar | ChemComp-NAG / |
Has ligand of interest | N |
-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 |
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Molecular weight | Value: 0.43 MDa / Experimental value: YES | ||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.5 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: BA.4/5 SARS-CoV-2 Spike bound to mouse ACE2 | ||||||||||||||||||||||||
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 FIELDBright-field microscopy / Nominal defocus max: 2800 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 58 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: dev_4827: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 103496 / Symmetry type: POINT | ||||||||||||||||||||||||
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