+Open data
-Basic information
Entry | Database: PDB / ID: 8uin | ||||||
---|---|---|---|---|---|---|---|
Title | Structure of the C3bBb-albicin complex | ||||||
Components |
| ||||||
Keywords | IMMUNE SYSTEM / Complement / Inhibitor / Mosquito / Convertase | ||||||
Function / homology | Function and homology information alternative-complement-pathway C3/C5 convertase / C5L2 anaphylatoxin chemotactic receptor binding / oviduct epithelium development / regulation of triglyceride biosynthetic process / positive regulation of activation of membrane attack complex / complement binding / vertebrate eye-specific patterning / positive regulation of apoptotic cell clearance / complement-mediated synapse pruning / Alternative complement activation ...alternative-complement-pathway C3/C5 convertase / C5L2 anaphylatoxin chemotactic receptor binding / oviduct epithelium development / regulation of triglyceride biosynthetic process / positive regulation of activation of membrane attack complex / complement binding / vertebrate eye-specific patterning / positive regulation of apoptotic cell clearance / complement-mediated synapse pruning / Alternative complement activation / positive regulation of lipid storage / positive regulation of phagocytosis, engulfment / positive regulation of G protein-coupled receptor signaling pathway / complement receptor mediated signaling pathway / Activation of C3 and C5 / positive regulation of type IIa hypersensitivity / positive regulation of D-glucose transmembrane transport / complement-dependent cytotoxicity / complement activation / complement activation, alternative pathway / endopeptidase inhibitor activity / neuron remodeling / B cell activation / amyloid-beta clearance / positive regulation of vascular endothelial growth factor production / Purinergic signaling in leishmaniasis infection / complement activation, classical pathway / Peptide ligand-binding receptors / fatty acid metabolic process / Regulation of Complement cascade / Post-translational protein phosphorylation / response to bacterium / positive regulation of receptor-mediated endocytosis / 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 / G alpha (i) signalling events / toxin activity / secretory granule lumen / blood microparticle / receptor ligand activity / inflammatory response / immune response / positive regulation of protein phosphorylation / G protein-coupled receptor signaling pathway / endoplasmic reticulum lumen / serine-type endopeptidase activity / signaling receptor binding / Neutrophil degranulation / cell surface / signal transduction / protein-containing complex / proteolysis / extracellular space / extracellular exosome / extracellular region / plasma membrane Similarity search - Function | ||||||
Biological species | Anopheles albimanus (mosquito) Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.86 Å | ||||||
Authors | Andersen, J.F. / Lei, H. | ||||||
Funding support | United States, 1items
| ||||||
Citation | Journal: Commun Biol / Year: 2024 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: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 8uin.cif.gz | 873.2 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb8uin.ent.gz | 662.8 KB | Display | PDB format |
PDBx/mmJSON format | 8uin.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8uin_validation.pdf.gz | 1.5 MB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 8uin_full_validation.pdf.gz | 1.5 MB | Display | |
Data in XML | 8uin_validation.xml.gz | 103 KB | Display | |
Data in CIF | 8uin_validation.cif.gz | 155.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ui/8uin ftp://data.pdbj.org/pub/pdb/validation_reports/ui/8uin | HTTPS FTP |
-Related structure data
Related structure data | 42300MC 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 , 4 types, 8 molecules CDJXAGBH
#1: Protein | Mass: 13461.331 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Anopheles albimanus (mosquito) / Production host: Escherichia coli BL21(DE3) (bacteria) / Variant (production host): pLysS / References: UniProt: A0A1Y9G8D0 #2: Protein | Mass: 25766.305 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P00751 #3: Protein | Mass: 71154.047 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P01024 #4: Protein | Mass: 104073.164 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P01024 |
---|
-Sugars , 2 types, 4 molecules
#5: 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 |
---|---|
#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 | Name: complex of C3bBb with the inhibitor albicin / Type: COMPLEX / Entity ID: #1-#4 / Source: MULTIPLE SOURCES |
---|---|
Molecular weight | Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.4 / Details: 10 mM Hepes pH 7.4, 150 mM NaCl, 5 mM MgCl2 |
Specimen | Conc.: 1.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: The sample was formed by incubating C3b, factor B, factor D and albicin. The sample was monodisperse |
Specimen support | Grid material: GOLD / Grid type: C-flat-1.2/1.3 |
Vitrification | Instrument: FEI VITROBOT MARK III / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 279.15 K |
-Electron microscopy imaging
Microscopy | Model: TFS GLACIOS |
---|---|
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2200 nm / Nominal defocus min: 300 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: 492352 | ||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C2 (2 fold cyclic) | ||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.86 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 65862 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | Space: REAL | ||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | 3D fitting-ID: 1 / Source name: PDB / Type: experimental model
| ||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
|