+Open data
-Basic information
Entry | Database: PDB / ID: 8wgv | ||||||
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Title | BA.2(S375) Spike (S6P)/hACE2 complex | ||||||
Components |
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Keywords | VIRAL PROTEIN/HYDROLASE / Complex / VIRAL PROTEIN-HYDROLASE complex | ||||||
Function / homology | Function and homology information 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 / tryptophan transport / positive regulation of gap junction assembly / regulation of systemic arterial blood pressure by renin-angiotensin / 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 / tryptophan transport / positive regulation of gap junction assembly / regulation of systemic arterial blood pressure by renin-angiotensin / regulation of vasoconstriction / regulation of cardiac conduction / peptidyl-dipeptidase activity / angiotensin maturation / maternal process involved in female pregnancy / Metabolism of Angiotensinogen to Angiotensins / metallocarboxypeptidase activity / Attachment and Entry / negative regulation of signaling receptor activity / carboxypeptidase activity / regulation of cytokine production / positive regulation of cardiac muscle contraction / viral life cycle / blood vessel diameter maintenance / negative regulation of smooth muscle cell proliferation / regulation of transmembrane transporter activity / brush border membrane / cilium / negative regulation of ERK1 and ERK2 cascade / endocytic vesicle membrane / metallopeptidase activity / positive regulation of reactive oxygen species metabolic process / virus receptor activity / regulation of cell population proliferation / regulation of inflammatory response / Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / endopeptidase activity / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / Potential therapeutics for SARS / 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 / symbiont entry into host cell / membrane raft / apical plasma membrane / fusion of virus membrane with host plasma membrane / endoplasmic reticulum lumen / fusion of virus membrane with host endosome membrane / viral envelope / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / 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 / extracellular exosome / zinc ion binding / extracellular region / membrane / identical protein binding / plasma membrane Similarity search - Function | ||||||
Biological species | Severe acute respiratory syndrome coronavirus 2 Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.92 Å | ||||||
Authors | Wei, X. / Zhang, Z. | ||||||
Funding support | China, 1items
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Citation | Journal: Nat Immunol / Year: 2024 Title: The receptor binding domain of SARS-CoV-2 Omicron subvariants targets Siglec-9 to decrease its immunogenicity by preventing macrophage phagocytosis. Authors: Xin He / Xiantao Zhang / Bolin Wu / Jieyi Deng / Yongli Zhang / Airu Zhu / Yaochang Yuan / Yingtong Lin / Achun Chen / Jinzhu Feng / Xiumei Wang / Shijian Wu / Yingying Liu / Jie Liu / Yalin ...Authors: Xin He / Xiantao Zhang / Bolin Wu / Jieyi Deng / Yongli Zhang / Airu Zhu / Yaochang Yuan / Yingtong Lin / Achun Chen / Jinzhu Feng / Xiumei Wang / Shijian Wu / Yingying Liu / Jie Liu / Yalin Wang / Rong Li / Chaofeng Liang / Quyu Yuan / Yu Liang / Qiannan Fang / Zhihui Xi / Wenjie Li / Liting Liang / Zhenglai Zhang / Hui Tang / Yi Peng / Changwen Ke / Xiancai Ma / Weibin Cai / Ting Pan / Bingfeng Liu / Kai Deng / Jun Chen / Jincun Zhao / Xuepeng Wei / Ran Chen / Yiwen Zhang / Hui Zhang / Abstract: The development of a vaccine specific to severe acute respiratory syndrome coronavirus 2 Omicron has been hampered due to its low immunogenicity. Here, using reverse mutagenesis, we found that a ...The development of a vaccine specific to severe acute respiratory syndrome coronavirus 2 Omicron has been hampered due to its low immunogenicity. Here, using reverse mutagenesis, we found that a phenylalanine-to-serine mutation at position 375 (F375S) in the spike protein of Omicron to revert it to the sequence found in Delta and other ancestral strains significantly enhanced the immunogenicity of Omicron vaccines. Sequence FAPFFAF at position 371-377 in Omicron spike had a potent inhibitory effect on macrophage uptake of receptor-binding domain (RBD) nanoparticles or spike-pseudovirus particles containing this sequence. Omicron RBD enhanced binding to Siglec-9 on macrophages to impair phagocytosis and antigen presentation and promote immune evasion, which could be abrogated by the F375S mutation. A bivalent F375S Omicron RBD and Delta-RBD nanoparticle vaccine elicited potent and broad nAbs in mice, rabbits and rhesus macaques. Our research suggested that manipulation of the Siglec-9 pathway could be a promising approach to enhance vaccine response. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8wgv.cif.gz | 854.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8wgv.ent.gz | 699.9 KB | Display | PDB format |
PDBx/mmJSON format | 8wgv.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wg/8wgv ftp://data.pdbj.org/pub/pdb/validation_reports/wg/8wgv | HTTPS FTP |
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-Related structure data
Related structure data | 37516MC 8wgwC 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: 138165.328 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Strain: Omicron/BA.2 / Gene: S, 2 / Production host: Homo sapiens (human) / References: UniProt: P0DTC2 #2: Protein | Mass: 70884.734 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ACE2, UNQ868/PRO1885 / Production host: Homo sapiens (human) References: UniProt: Q9BYF1, angiotensin-converting enzyme 2, Hydrolases; Acting on peptide bonds (peptidases); Metallocarboxypeptidases #3: Polysaccharide | #4: Sugar | ChemComp-NAG / Has ligand of interest | 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: BA.2(S375) Spike (S6P)/hACE2 complex / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.5 |
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 FIELDBright-field microscopy / Nominal defocus max: 2500 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 2.92 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 74518 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | PDB-ID: 7XO8 Accession code: 7XO8 / Source name: PDB / Type: experimental model | ||||||||||||||||||||||||
Refine LS restraints |
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