C3 Human
Description
Activation Pathways and Functional Roles
C3 is central to classical, lectin, and alternative pathways, with its activation amplified by C3 convertases (C4b2a or C3bBb). Key processes include:
Classical Pathway Activation
Alternative Pathway Amplification
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C3bBb convertase cleaves C3 → C3a + C3b, creating a feedback loop .
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C3b covalently attaches to pathogens via its thioester bond .
Lectin Pathway
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MBL-CASPR (mannose-binding lectin-associated serine proteases) activate C3 similarly to the classical pathway .
Clinical Significance and Diagnostic Applications
C3 levels are measured in plasma to diagnose complement-related disorders:
Diagnostic Use:
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Low C3: Indicative of active complement consumption (e.g., SLE, glomerulonephritis) .
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Normal C3: Excludes complement-mediated diseases but may occur in early-stage or chronic conditions .
Inhibitors and Drug Targets
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Compstatin: A cyclic peptide binding C3 to block convertase formation. Derivatives (e.g., Cp20, AMY-101) show improved potency in preclinical models of AMD and kidney disease .
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Recombinant C3 Derivatives: Engineered C3-CVF hybrids (e.g., Cobra Venom Factor) stabilize C3 convertase, enabling sustained complement inactivation. These avoid immunogenicity of exogenous proteins .
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siRNA Therapeutics: SGB-9768 (Sanegene) reduces C3 mRNA, lowering plasma C3 levels by >90% in Phase I trials. Targets include IgA nephropathy and dry AMD .
Emerging Insights and Challenges
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Homeostatic Roles: C3 modulates synaptic pruning, tissue regeneration, and tumor surveillance .
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Pathogen Evasion: Viruses (e.g., HIV, HBV) exploit C3 regulators (e.g., Factor H) to evade immune detection .
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Therapeutic Challenges: Systemic C3 inhibition risks immunosuppression, necessitating tissue-specific targeting .
Product Specs
Human C3, a naturally glycosylated polypeptide with two disulfide-linked chains, plays a pivotal role in activating all three complement pathways. Each pathway's initiation generates proteolytic enzyme complexes that bind to target surfaces. These enzymes cleave C3, releasing the anaphylatoxin C3a and activating C3b. Due to its thioester reaction with water, a significant portion of activated C3 doesn't bind to the surface, forming fluid phase C3b, rapidly inactivated by factors H and I into iC3b. Surface-bound C3b is crucial across all pathways for efficient C5 activation and the formation of C5b-9 complexes, which lyse target cell membranes.
Human Complement C3, derived from human plasma, has a molecular weight of 185 kDa.
The product is a sterile filtered solution.
The C3 solution is prepared in phosphate buffer saline.
Human C3 remains stable for 2-4 weeks when stored at 4°C. For extended storage, freeze below -20°C. Adding a carrier protein (0.1% HSA or BSA) is recommended for long-term storage. Avoid repeated freezing and thawing.
The purity is determined to be greater than 94.0% using SDS-PAGE analysis.
The plasma used in this product has undergone rigorous testing and is confirmed negative for antibodies against HIV-1, HIV-2, HCV, HTLV-I/II, STS, and HBSAg.
Complement C3, C3 and PZP-like alpha-2-macroglobulin domain-containing protein 1, C3, CPAMD1.
Human Plasma.
Q&A
Here’s a structured collection of FAQs for researchers studying "C3 Human," focusing on academic research scenarios. The questions and answers integrate methodological rigor, experimental design principles, and data analysis strategies aligned with scientific research standards.
What experimental methodologies are recommended for detecting C3 Human in serum samples?
To detect C3 Human in serum, use immunoassays such as:
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ELISA (enzyme-linked immunosorbent assay) with monoclonal antibodies specific to C3 epitopes.
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Western blotting to confirm molecular weight (~185 kDa for full-length C3).
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Flow cytometry for cell-surface C3 detection in immune cells.
Key considerations:
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Pre-treat samples with protease inhibitors to prevent degradation.
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Include controls for spontaneous C3 activation (e.g., EDTA-treated samples).
How do researchers reconcile contradictory data on C3 Human’s role in inflammatory responses?
Contradictions often arise from:
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Model system variability (e.g., murine vs. human cell lines).
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Temporal factors (acute vs. chronic inflammation).
Methodological approach:
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Conduct meta-analyses of peer-reviewed studies (e.g., PRISMA guidelines).
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Perform time-course experiments to track C3 expression dynamics.
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Use knockout models (e.g., CRISPR-Cas9-edited cell lines) to isolate C3-specific effects.
What statistical frameworks are optimal for analyzing C3 Human interaction networks?
For interaction studies (e.g., C3-complement receptor binding):
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Bayesian network analysis to infer probabilistic relationships.
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Structural equation modeling (SEM) for pathway validation.
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Cluster analysis (e.g., k-means) to group co-regulated genes/proteins.
Data integration tool:
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DIABLO (mixOmics package in R) for cross-omics correlation analysis.
Table 1: Multi-omics markers linked to C3 dysregulation in lupus:
| Omics Layer | Marker | Association with C3 |
|---|---|---|
| Transcriptomic | C3↑ | 2.5-fold upregulation (q < 0.01) |
| Proteomic | C3a ↓ | Reduced anaphylatoxin in flares |
| Epigenetic | C3 promoter hypomethylation | 40% loss in methylation (vs. controls) |
What in silico models predict C3 Human’s structural stability under pathogenic mutations?
Use molecular dynamics (MD) simulations:
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Software: GROMACS or AMBER.
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Parameters: Solvate mutant C3 structures, run 100-ns simulations, analyze RMSD/RMSF.
Validation steps:
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Compare predicted stability with clinical variant databases (e.g., ClinVar).
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Validate via surface plasmon resonance (SPR) for binding affinity changes.
Which in vivo models best recapitulate C3 Human’s role in age-related macular degeneration (AMD)?
Model selection criteria:
| Model | Strengths | Limitations |
|---|---|---|
| C3-knockout mice | Clear phenotype (drusen accumulation) | Limited translatability to human AMD |
| Patient-derived iPSCs | Human-specific pathways | High cost/complexity |
| Non-human primates | Closest to human physiology | Ethical/logistical constraints |
Method recommendation: Use conditional knockout mice with retina-specific C3 depletion.
Methodological Guidelines for Data Contradiction Analysis
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Root-cause analysis: Audit experimental protocols (e.g., antibody lot variability).
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Sensitivity analysis: Test hypotheses across multiple assays (e.g., ELISA vs. mass spectrometry).
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Collaborative replication: Share datasets via platforms like Zenodo for independent validation.
Product Science Overview
C3 is the most abundant and essential protein in the complement system. It plays a pivotal role in both the classical and alternative pathways of complement activation. When the immune system detects harmful substances, C3 is activated and undergoes a conformational change, leading to its cleavage into two fragments: C3a and C3b .
- C3a: Acts as an anaphylatoxin, which means it can induce inflammation by increasing vascular permeability and attracting immune cells to the site of infection.
- C3b: Functions as an opsonin, marking pathogens for destruction by phagocytes. It also forms part of the C5 convertase complex, which is crucial for the formation of the membrane attack complex (MAC) that can lyse pathogens .
Research into C3 and its pathways has significant therapeutic potential. Understanding the mechanisms of C3 activation and regulation can lead to the development of treatments for autoimmune diseases, infections, and other immune-related conditions. Recombinant forms of C3 are also being explored for their potential in therapeutic applications.
