Serum amyloid A-3 protein

Overview

Serum amyloid A-3 protein (SAA3) is a major acute-phase protein primarily expressed in bovine mammary epithelial cells during inflammation. Unlike other SAA isoforms, SAA3 shows tissue-specific expression and plays a crucial role in local immune defense mechanisms.

This entry represents the bovine SAA3 protein, which serves as a reference for comparative studies with donkey milk proteins. Understanding the structural and functional characteristics of bovine SAA3 helps elucidate the unique properties of donkey milk proteins in hypoallergenic formulations.

Biological Function

Major acute phase reactant. SAA3 is an isoform of Serum Amyloid A that is significantly upregulated during inflammation and infection (e.g., mastitis).

In the context of milk, SAA3 is expressed in the mammary epithelial cells and secreted into colostrum. It exhibits antimicrobial activity against Gram-negative bacteria (e.g., E. coli) and Gram-positive bacteria (e.g., Streptococcus uberis). It may play a crucial role in the local defense of the mammary gland and the gastrointestinal protection of the neonate.

Gene Ontology (GO) Annotations

Sequence Information

Structure

The SAA3 protein adopts a typical four-helix bundle structure characteristic of the serum amyloid A family. The N-terminal region contains a highly conserved motif (TFLK) that is critical for receptor binding and antimicrobial activity.

AlphaFold predictions show high confidence scores (>90%) for the core structural elements. The protein is predominantly α-helical with a flexible C-terminal region that may be involved in lipid binding and oligomerization.

Expression

Tissue-specific expression: SAA3 is primarily expressed in mammary epithelial cells, especially during lactation and inflammation. It is also detected in other mucosal tissues but at lower levels.

Regulation: Expression is strongly induced by pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α. In bovine mammary tissue, SAA3 levels can increase over 100-fold during mastitis infection.

Milk concentration: In colostrum, SAA3 concentrations range from 10-50 μg/mL, decreasing to 1-5 μg/mL in mature milk. During mastitis, concentrations can exceed 200 μg/mL.

Homology

Species comparison: Bovine SAA3 shares approximately 65-70% sequence identity with equine SAA isoforms and 60-65% with human SAA1/SAA2. The N-terminal antimicrobial domain shows higher conservation across species.

Donkey milk comparison: Preliminary studies suggest donkey milk contains SAA-like proteins with similar antimicrobial functions but different antigenic properties. The lower sequence homology may contribute to donkey milk's hypoallergenic nature.

References

1. Molenaar AJ, et al. (2009) Acute phase proteins in bovine milk in an experimental model of Staphylococcus aureus subclinical mastitis. J Dairy Sci 92(3): 1178-1191.

2. McDonald TL, et al. (2001) Bovine serum amyloid A3 gene structure and promoter analysis. J Biol Chem 276(21): 17762-17768.

3. Larson MA, et al. (2005) Bovine serum amyloid A3 gene expression in mammary epithelial cells. Vet Immunol Immunopathol 107(3-4): 235-244.

4. Eckersall PD, et al. (2006) Acute phase proteins in bovine milk. J Vet Med B Infect Dis Vet Public Health 53(7): 317-323.