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Open data
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Basic information
Entry | Database: PDB / ID: 8btb | ||||||||||||
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Title | Hexameric human IgG3 Fc complex | ||||||||||||
![]() | (FLJ00385 protein (Fragment)) x 2 | ||||||||||||
![]() | IMMUNE SYSTEM / IgG3 / antibody / Fc hexamer | ||||||||||||
Function / homology | ![]() immunoglobulin complex, circulating / immunoglobulin receptor binding / complement activation, classical pathway / antigen binding / antibacterial humoral response / blood microparticle / extracellular exosome / plasma membrane Similarity search - Function | ||||||||||||
Biological species | ![]() | ||||||||||||
Method | ELECTRON MICROSCOPY / subtomogram averaging / cryo EM / Resolution: 14 Å | ||||||||||||
![]() | Abendstein, L. / Sharp, T.H. | ||||||||||||
Funding support | European Union, ![]()
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![]() | ![]() Title: Complement is activated by elevated IgG3 hexameric platforms and deposits C4b onto distinct antibody domains. Authors: Leoni Abendstein / Douwe J Dijkstra / Rayman T N Tjokrodirijo / Peter A van Veelen / Leendert A Trouw / Paul J Hensbergen / Thomas H Sharp / ![]() Abstract: IgG3 is unique among the IgG subclasses due to its extended hinge, allotypic diversity and enhanced effector functions, including highly efficient pathogen neutralisation and complement activation. ...IgG3 is unique among the IgG subclasses due to its extended hinge, allotypic diversity and enhanced effector functions, including highly efficient pathogen neutralisation and complement activation. It is also underrepresented as an immunotherapeutic candidate, partly due to a lack of structural information. Here, we use cryoEM to solve structures of antigen-bound IgG3 alone and in complex with complement components. These structures reveal a propensity for IgG3-Fab clustering, which is possible due to the IgG3-specific flexible upper hinge region and may maximise pathogen neutralisation by forming high-density antibody arrays. IgG3 forms elevated hexameric Fc platforms that extend above the protein corona to maximise binding to receptors and the complement C1 complex, which here adopts a unique protease conformation that may precede C1 activation. Mass spectrometry reveals that C1 deposits C4b directly onto specific IgG3 residues proximal to the Fab domains. Structural analysis shows this to be caused by the height of the C1-IgG3 complex. Together, these data provide structural insights into the role of the unique IgG3 extended hinge, which will aid the development and design of upcoming immunotherapeutics based on IgG3. | ||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 419.5 KB | Display | ![]() |
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PDB format | ![]() | 337.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1 MB | Display | ![]() |
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Full document | ![]() | 1.1 MB | Display | |
Data in XML | ![]() | 86.9 KB | Display | |
Data in CIF | ![]() | 130.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 16227MC 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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1 |
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Components
#1: Protein | Mass: 23768.957 Da / Num. of mol.: 6 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #2: Protein | Mass: 23782.943 Da / Num. of mol.: 6 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: subtomogram averaging |
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Sample preparation
Component | Name: Fc domain of human IgG3 / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 7.4 / Details: PBS |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
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Microscopy | Model: FEI TECNAI ARCTICA |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 6000 nm / Nominal defocus min: 3000 nm |
Image recording | Electron dose: 1.5 e/Å2 / Avg electron dose per subtomogram: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING ONLY | ||||||||||||||||||||||||
Symmetry | Point symmetry: C6 (6 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 14 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 571 / Symmetry type: POINT | ||||||||||||||||||||||||
EM volume selection | Num. of tomograms: 60 / Num. of volumes extracted: 1193 | ||||||||||||||||||||||||
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