β-Lactoglobulin

The major protein in whey is β-lactoglobulin, followed by α-lactalbumin (β-lactoglobulin ≈⁠ ⁠65%, α-lactalbumin ≈⁠⁠ ⁠25%, serum albumin ≈⁠⁠ ⁠8%, other ≈⁠ ⁠2%). β-lactoglobulin is a lipocalin protein able to bind many hydrophobic molecules, suggesting its role in their transport. BLG has also been shown to bind molecular iron via siderophores,^[8] indicating a possible role in immune pathways combatting pathogens; upon ingestion, BLG can shuttle complexed iron to immune cells, providing micronutrition to the cells, thus participating in overall immune tolerance.^[9][10] A human homologue of β-lactoglobulin is lacking in breast milk.^[11]

Due to its relative abundance in cow's milk and ease of purification, β-lactoglobulin has been the subject of substantial biophysical study; in particular, due to its significance to the food industry - where its physical properties can be either advantageous or disadvantageous to the manufacture and processing of dairy products.^[12] The structure of BLG has been circumscribed several times by X-ray crystallography and NMR,^[13] with several BLG variants identified, notably the primary bovine variants labelled β-lactoglobulin "A" and "B".

Bovine β-lactoglobulin is a relatively small protein, consisting 162 residues, amounting to18.4 kDa. NMR analysis of BLG in physiological conditions has determined the protein is predominantly dimeric, dissociating to a monomer in acidic environments below pH 3, while preserving its native state.^[14] Conversely, BLG also occurs in tetrameric,^[15] octameric^[16] and other multimeric^[17] aggregation forms in a variety of natural conditions.

In solution, β-Lactoglobulin forms gels in several conditions, particularly when its native structure is sufficiently destabilised to allow aggregation.^[18] For example, after prolonged heat at low pH and low ionic strength, a transparent `fine-stranded' gel is formed by assembly of protein molecules into long stiff fibres. Folding intermediates of the BLG protein can be studied using light spectroscopy and a denaturing solvent, yielding an unusual but important intermediate composed purely of α-helices - despite its native β-sheet structure. This phenomena is suggested to indicate evolutionary selection for the helical intermediate, avoiding aggregation during the folding process.^[19]

β-Lactoglobulin is the main component of milk skin - formed by coagulation and denaturing when milk boils. Once denatured, the BLG proteins form a thin, gelatinous film on the surface of the liquid milk.

Due to the allergenic potential of cow's milk (i.e., lactose intolerance),^[6] manufacturers in European Union are required to evidence the presence or absence of β-lactoglobulin on labels for food products containing milk to satisfy the requirements of the EC Directive; this is typically determined by food testing laboratories using enzyme linked immunosorbent assay to identify and quantify the BLG in said products.

Although β-lactoglobulin is considered a major allergen, the protective effects of consuming raw cow's milk - namely its ability to transport micronutrients - has been shown to depend on the protein content of the whey fraction, thus of β-lactoglobulin.^[20] Studies have shown that BLG carrying micronutrients acted as a tolerogen, protecting against allergy development. However, when micronutrients were absent, BLG acted as an allergen.^[21][22][23] Laboratory polymerization of β-lactoglobulin by microbial transglutaminase can reduce its allergenic potential in both children and adults with an IgE-mediated cow's milk allergy.^[24]

• Casein