+Open data
-Basic information
Entry | Database: PDB / ID: 8xxw | ||||||
---|---|---|---|---|---|---|---|
Title | Fab M2-7 complexed with SARS-Cov2 RBD and human ACE2 | ||||||
Components |
| ||||||
Keywords | ANTIVIRAL PROTEIN/IMMUNE SYSTEM / antibody viral protein complex / IMMUNE SYSTEM/VIRAL PROTEIN / ANTIVIRAL PROTEIN / ANTIVIRAL PROTEIN-IMMUNE SYSTEM 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 / 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 / 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 / Induction of Cell-Cell Fusion / Potential therapeutics for SARS / 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 | Homo sapiens (human) Severe acute respiratory syndrome coronavirus 2 Mus musculus (house mouse) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.03 Å | ||||||
Authors | Liu, C. / Xie, Y. | ||||||
Funding support | China, 1items
| ||||||
Citation | Journal: Cell Rep / Year: 2024 Title: Mosaic RBD nanoparticle elicits immunodominant antibody responses across sarbecoviruses. Authors: Chuanyu Liu / Senyu Xu / Yuxuan Zheng / Yufeng Xie / Kun Xu / Yan Chai / Tingrong Luo / Lianpan Dai / George F Gao / Abstract: Nanoparticle vaccines displaying mosaic receptor-binding domains (RBDs) or spike (S) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or other sarbecoviruses are used in ...Nanoparticle vaccines displaying mosaic receptor-binding domains (RBDs) or spike (S) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or other sarbecoviruses are used in preparedness against potential zoonotic outbreaks. Here, we describe a self-assembling nanoparticle using lumazine synthase (LuS) as the scaffold to display RBDs from different sarbecoviruses. Mosaic nanoparticles induce sarbecovirus cross-neutralizing antibodies comparable to a nanoparticle cocktail. We find mosaic nanoparticles elicit a B cell receptor repertoire using an immunodominant germline gene pair of IGHV14-3:IGKV14-111. Most of the tested IGHV14-3:IGKV14-111 monoclonal antibodies (mAbs) are broadly cross-reactive to clade 1a, 1b, and 3 sarbecoviruses. Using mAb competition and cryo-electron microscopy, we determine that a representative IGHV14-3:IGKV14-111 mAb, M2-7, binds to a conserved epitope on the RBD, largely overlapping with the pan-sarbecovirus mAb S2H97. This suggests mosaic nanoparticles expand B cell recognition of the common epitopes shared by different clades of sarbecoviruses. These results provide immunological insights into the cross-reactive responses elicited by mosaic nanoparticles against sarbecoviruses. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 8xxw.cif.gz | 204.2 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb8xxw.ent.gz | 158.8 KB | Display | PDB format |
PDBx/mmJSON format | 8xxw.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8xxw_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 8xxw_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 8xxw_validation.xml.gz | 39.5 KB | Display | |
Data in CIF | 8xxw_validation.cif.gz | 56.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/xx/8xxw ftp://data.pdbj.org/pub/pdb/validation_reports/xx/8xxw | HTTPS FTP |
-Related structure data
Related structure data | 38763MC M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
-Protein , 2 types, 2 molecules AE
#1: Protein | Mass: 67310.727 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ACE2, UNQ868/PRO1885 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: Q9BYF1 |
---|---|
#2: Protein | Mass: 20354.734 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 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: P0DTC2 |
-Antibody , 2 types, 2 molecules HL
#3: Antibody | Mass: 13359.830 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Cell line (production host): HEK293 / Production host: Homo sapiens (human) |
---|---|
#4: Antibody | Mass: 12046.495 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Cell line (production host): HEK293 / Production host: Homo sapiens (human) |
-Non-polymers / Sugars , 2 types, 4 molecules
#5: Chemical | ChemComp-ZN / |
---|---|
#6: Sugar |
-Details
Has ligand of interest | N |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component |
| ||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Source (natural) |
| ||||||||||||||||||||||||||||||
Source (recombinant) | Organism: Homo sapiens (human) | ||||||||||||||||||||||||||||||
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 |
---|---|
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 (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
3D reconstruction | Resolution: 3.03 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 86429 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
|