+
Open data
-
Basic information
Entry | Database: PDB / ID: 8uh2 | ||||||
---|---|---|---|---|---|---|---|
Title | Complex of C3b with the inhibitor albicin | ||||||
![]() |
| ||||||
![]() | IMMUNE SYSTEM / Complement / Mosquito / C3 / convertase / alternative pathway | ||||||
Function / homology | ![]() C5L2 anaphylatoxin chemotactic receptor binding / oviduct epithelium development / regulation of triglyceride biosynthetic process / positive regulation of activation of membrane attack complex / vertebrate eye-specific patterning / positive regulation of apoptotic cell clearance / complement-mediated synapse pruning / Alternative complement activation / Activation of C3 and C5 / positive regulation of phagocytosis, engulfment ...C5L2 anaphylatoxin chemotactic receptor binding / oviduct epithelium development / regulation of triglyceride biosynthetic process / positive regulation of activation of membrane attack complex / vertebrate eye-specific patterning / positive regulation of apoptotic cell clearance / complement-mediated synapse pruning / Alternative complement activation / Activation of C3 and C5 / positive regulation of phagocytosis, engulfment / positive regulation of lipid storage / positive regulation of G protein-coupled receptor signaling pathway / positive regulation of type IIa hypersensitivity / complement receptor mediated signaling pathway / complement-dependent cytotoxicity / positive regulation of D-glucose transmembrane transport / complement activation / complement activation, alternative pathway / endopeptidase inhibitor activity / neuron remodeling / amyloid-beta clearance / B cell activation / positive regulation of vascular endothelial growth factor production / complement activation, classical pathway / Purinergic signaling in leishmaniasis infection / Peptide ligand-binding receptors / Regulation of Complement cascade / response to bacterium / Post-translational protein phosphorylation / fatty acid metabolic process / positive regulation of receptor-mediated endocytosis / positive regulation of protein phosphorylation / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / positive regulation of angiogenesis / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / azurophil granule lumen / toxin activity / blood microparticle / G alpha (i) signalling events / secretory granule lumen / immune response / G protein-coupled receptor signaling pathway / receptor ligand activity / inflammatory response / endoplasmic reticulum lumen / signaling receptor binding / Neutrophil degranulation / cell surface / signal transduction / protein-containing complex / extracellular space / extracellular exosome / extracellular region / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.59 Å | ||||||
![]() | Andersen, J.F. / Lei, H. / Strayer, E. / Ribeiro, J.M. | ||||||
Funding support | ![]()
| ||||||
![]() | ![]() Title: Mechanism of complement inhibition by a mosquito protein revealed through cryo-EM. Authors: John F Andersen / Haotian Lei / Ethan C Strayer / Van Pham / José M C Ribeiro / ![]() Abstract: Salivary complement inhibitors occur in many of the blood feeding arthropod species responsible for transmission of pathogens. During feeding, these inhibitors prevent the production of ...Salivary complement inhibitors occur in many of the blood feeding arthropod species responsible for transmission of pathogens. During feeding, these inhibitors prevent the production of proinflammatory anaphylatoxins, which may interfere with feeding, and limit formation of the membrane attack complex which could damage arthropod gut tissues. Salivary inhibitors are, in many cases, novel proteins which may be pharmaceutically useful or display unusual mechanisms that could be exploited pharmaceutically. Albicin is a potent inhibitor of the alternative pathway of complement from the saliva of the malaria transmitting mosquito, Anopheles albimanus. Here we describe the cryo-EM structure of albicin bound to C3bBb, the alternative C3 convertase, a proteolytic complex that is responsible for cleavage of C3 and amplification of the complement response. Albicin is shown to induce dimerization of C3bBb, in a manner similar to the bacterial inhibitor SCIN, to form an inactive complex unable to bind the substrate C3. Size exclusion chromatography and structures determined after 30 minutes of incubation of C3b, factor B (FB), factor D (FD) and albicin indicate that FBb dissociates from the inhibited dimeric complex leaving a C3b-albicin dimeric complex which apparently decays more slowly. | ||||||
History |
|
-
Structure visualization
Structure viewer | Molecule: ![]() ![]() |
---|
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 768.8 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 576.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.3 MB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 1.4 MB | Display | |
Data in XML | ![]() | 92.2 KB | Display | |
Data in CIF | ![]() | 140.1 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 42244MC ![]() 8uinC M: map data used to model this data C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
Components
#1: Protein | Mass: 13461.331 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Details: Inhibitor of complement / Source: (gene. exp.) ![]() ![]() ![]() ![]() #2: Protein | Mass: 71154.047 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() #3: Protein | Mass: 104073.164 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() #4: Sugar | ChemComp-NAG / Has ligand of interest | N | Has protein modification | Y | |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
Component |
| ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Molecular weight | Experimental value: NO | ||||||||||||||||||||||||
Source (natural) |
| ||||||||||||||||||||||||
Source (recombinant) | Organism: ![]() ![]() | ||||||||||||||||||||||||
Buffer solution | pH: 7.4 | ||||||||||||||||||||||||
Specimen | Conc.: 1.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: Complex was formed by incubation of C3b, Factor B, Factor D and albicin in vitro and was monodisperse | ||||||||||||||||||||||||
Specimen support | Grid material: GOLD / Grid type: C-flat-1.2/1.3 | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-
Electron microscopy imaging
Microscopy | Model: TFS GLACIOS |
---|---|
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 500 nm |
Image recording | Electron dose: 66.7 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-
Processing
EM software |
| ||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 147624 | ||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C2 (2 fold cyclic) | ||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.59 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 52781 / Algorithm: FOURIER SPACE / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
|