β-Lactoglobulin (beta-lactoglobulin, BLG, Bos d 5) is the major whey protein of cow and sheep's milk (~3 g/L), and is also present in many other mammalian species; a notable exception being humans. Its structure, properties and biological role have been reviewed many times. BLG is considered to be a milk allergen.

Function

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, 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. A human homologue of β-lactoglobulin is lacking in breast milk.

Structure

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. The structure of BLG has been circumscribed several times by X-ray crystallography and NMR,; 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 of 162 residues, amounting to 18.4 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. Conversely, BLG also occurs in tetrameric, octameric and other multimeric 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. 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.

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.

Clinical significance

Due to the allergenic potential of cow's milk (i.e., lactose intolerance),listed in Annex IIIa of Directive 2000/13/EC 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. 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. 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.

Biotechnology Cow breeding In 2018, the first genetically modified cows without β-Lactoglobulin-producing genes were produced by zygotic deletion of the BLG gene locus. Ongoing study aims to produce raw milk without the BLG allergen.

Recombinant production In September 2023, the European Innovation Council funded a "Hydrocow" project, by Solar Foods, aiming to produce BLG with the help of Xanthobacter hydrogen-oxidizing bacteria, carbon dioxide and electricity.

See also

Casein

References