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Yorodumi- PDB-8kc2: Cryo-EM structure of SARS-CoV-2 BA.3 RBD in complex with golden h... -
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-Basic information
Entry | Database: PDB / ID: 8kc2 | ||||||
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Title | Cryo-EM structure of SARS-CoV-2 BA.3 RBD in complex with golden hamster ACE2 (local refinement) | ||||||
Components |
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Keywords | VIRAL PROTEIN/HYDROLASE / SARS-CoV-2 / BA.3 / spike protein / VIRAL PROTEIN / HYDROLASE-VIRAL PROTEIN complex / VIRAL PROTEIN-HYDROLASE complex | ||||||
Function / homology | Function and homology information Hydrolases; Acting on peptide bonds (peptidases) / positive regulation of L-proline import across plasma membrane / angiotensin-mediated drinking behavior / tryptophan transport / positive regulation of gap junction assembly / regulation of cardiac conduction / peptidyl-dipeptidase activity / carboxypeptidase activity / positive regulation of cardiac muscle contraction / brush border membrane ...Hydrolases; Acting on peptide bonds (peptidases) / positive regulation of L-proline import across plasma membrane / angiotensin-mediated drinking behavior / tryptophan transport / positive regulation of gap junction assembly / regulation of cardiac conduction / peptidyl-dipeptidase activity / carboxypeptidase activity / positive regulation of cardiac muscle contraction / brush border membrane / cilium / metallopeptidase activity / virus receptor activity / endopeptidase activity / Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / 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 / Attachment and Entry / membrane fusion / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / symbiont-mediated suppression of host innate immune response / 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 / identical protein binding / membrane / metal ion binding / plasma membrane / cytoplasm Similarity search - Function | ||||||
Biological species | Mesocricetus auratus (golden hamster) Severe acute respiratory syndrome coronavirus 2 | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.6 Å | ||||||
Authors | Niu, S. / Zhao, Z.N. / Chai, Y. / Gao, G.F. | ||||||
Funding support | China, 1items
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Citation | Journal: J Virol / Year: 2024 Title: Structural basis and analysis of hamster ACE2 binding to different SARS-CoV-2 spike RBDs. Authors: Sheng Niu / Zhennan Zhao / Zhimin Liu / Xiaoyu Rong / Yan Chai / Bin Bai / Pengcheng Han / Guijun Shang / Jianle Ren / Ying Wang / Xin Zhao / Kefang Liu / Wen-Xia Tian / Qihui Wang / George Fu Gao / Abstract: Pet golden hamsters were first identified being infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delta variant of concern (VOC) and transmitted the virus back to humans ...Pet golden hamsters were first identified being infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delta variant of concern (VOC) and transmitted the virus back to humans in Hong Kong in January 2022. Here, we studied the binding of two hamster (golden hamster and Chinese hamster) angiotensin-converting enzyme 2 (ACE2) proteins to the spike protein receptor-binding domains (RBDs) of SARS-CoV-2 prototype and eight variants, including alpha, beta, gamma, delta, and four omicron sub-variants (BA.1, BA.2, BA.3, and BA.4/BA.5). We found that the two hamster ACE2s present slightly lower affinity for the RBDs of all nine SARS-CoV-2 viruses tested than human ACE2 (hACE2). Furthermore, the similar infectivity to host cells expressing hamster ACE2s and hACE2 was confirmed with the nine pseudotyped SARS-CoV-2 viruses. Additionally, we determined two cryo-electron microscopy (EM) complex structures of golden hamster ACE2 (ghACE2)/delta RBD and ghACE2/omicron BA.3 RBD. The residues Q34 and N82, which exist in many rodent ACE2s, are responsible for the lower binding affinity of ghACE2 compared to hACE2. These findings suggest that all SARS-CoV-2 VOCs may infect hamsters, highlighting the necessity of further surveillance of SARS-CoV-2 in these animals.IMPORTANCESARS-CoV-2 can infect many domestic animals, including hamsters. There is an urgent need to understand the binding mechanism of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants to hamster receptors. Herein, we showed that two hamster angiotensin-converting enzyme 2s (ACE2s) (golden hamster ACE2 and Chinese hamster ACE2) can bind to the spike protein receptor-binding domains (RBDs) of SARS-CoV-2 prototype and eight variants and that pseudotyped SARS-CoV-2 viruses can infect hamster ACE2-expressing cells. The binding pattern of golden hamster ACE2 to SARS-CoV-2 RBDs is similar to that of Chinese hamster ACE2. The two hamster ACE2s present slightly lower affinity for the RBDs of all nine SARS-CoV-2 viruses tested than human ACE2. We solved the cryo-electron microscopy (EM) structures of golden hamster ACE2 in complex with delta RBD and omicron BA.3 RBD and found that residues Q34 and N82 are responsible for the lower binding affinity of ghACE2 compared to hACE2. Our work provides valuable information for understanding the cross-species transmission mechanism of SARS-CoV-2. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8kc2.cif.gz | 155.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8kc2.ent.gz | 119.8 KB | Display | PDB format |
PDBx/mmJSON format | 8kc2.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8kc2_validation.pdf.gz | 513.4 KB | Display | wwPDB validaton report |
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Full document | 8kc2_full_validation.pdf.gz | 519.1 KB | Display | |
Data in XML | 8kc2_validation.xml.gz | 16.6 KB | Display | |
Data in CIF | 8kc2_validation.cif.gz | 24.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/kc/8kc2 ftp://data.pdbj.org/pub/pdb/validation_reports/kc/8kc2 | HTTPS FTP |
-Related structure data
Related structure data | 37090MC 8ka8C 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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-Components
#1: Protein | Mass: 68943.328 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mesocricetus auratus (golden hamster) / Gene: Ace2 / Production host: Homo sapiens (human) References: UniProt: A0A1U7QTA1, Hydrolases; Acting on peptide bonds (peptidases) | ||
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#2: Protein | Mass: 22072.924 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Gene: S, 2 / Production host: Homo sapiens (human) / References: UniProt: P0DTC2 | ||
#3: 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 | ||
#4: Chemical | ChemComp-ZN / | ||
#5: Sugar | Has ligand of interest | Y | |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
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Source (recombinant) |
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Buffer solution | pH: 8 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
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: 2000 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
CTF correction | Type: NONE | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 2.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 416754 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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