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Open data
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Basic information
Entry | Database: PDB / ID: 8aqs | ||||||
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Title | BA.4/5 SARS-CoV-2 Spike bound to human ACE2 (local) | ||||||
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![]() | VIRAL PROTEIN / SARS-COV2 / omicron / Spike / RBD / mouse / ACE2 / ANTIVIRAL PROTEIN / BA4/5 | ||||||
Function / homology | ![]() 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 / virion component / 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 | ![]() ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.92 Å | ||||||
![]() | Lau, K. / Ni, D. / Beckert, B. / Nazarov, S. / Myasnikov, A. / Pojer, F. / Stahlberg, H. / Uchikawa, E. | ||||||
Funding support | ![]()
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![]() | ![]() 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: ![]() 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: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 204.2 KB | Display | ![]() |
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PDB format | ![]() | 145.1 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.5 MB | Display | ![]() |
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Full document | ![]() | 1.5 MB | Display | |
Data in XML | ![]() | 40.5 KB | Display | |
Data in CIF | ![]() | 58.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 15588MC ![]() 8aqtC ![]() 8aquC ![]() 8aqvC ![]() 8aqwC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 142688.062 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() Gene: S, 2, wac / Production host: ![]() ![]() | ||||||
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#2: Protein | Mass: 101941.320 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() | ||||||
#3: Sugar | ChemComp-NAG / #4: Chemical | ChemComp-ZN / | #5: Water | ChemComp-HOH / | 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 |
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Sample preparation
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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 human ACE2 | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD / 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) |
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Processing
Software | Name: PHENIX / Version: dev_4827: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.92 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 94718 / Symmetry type: POINT | ||||||||||||||||||||||||
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