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β-Lactoglobulin (β-LG) was first isolated in 1934.<ref>http://www.jbc.org/content/104/2/359.citation</ref> It is a main globular protein which was isolated from whey, a by-product from cow milk-cheese manufacture. Cow milk itself contains 20% whey proteins and 80% casein protein. β-Lactoglobulin constitutes 50-65% dry solids whey protein or 12% of whole cow milk proteins.  

Due to its abundance, cheap and relatively easy to isolate nature, β-Lactoglobulin used widely in Industry to increase the protein contents of the food and beverage products.  

Bovine β-lactoglobulin (β-Lg) is a much biochemically and structurally  studied and commercially important whey protein with an as yet undetermined function, although it is of obvious nutritional value. β-Lg binds a variety of ligands and by comparison of the general structures of these molecules together with several competition studies, it appears that there are at least 3 independent binding sites: calyx, putative grove, and dimer interface (Fig. 2).<ref>http://www.sciencedirect.com/science/article/pii/S0958694698000211</ref><ref>PMID:9867826</ref>

β-Lactoglobulin amino-acid sequence and 3-dimensional structure show that it belongs to [[Lipocalin]] family which capable of binding hydrophobic ligandsand  thus may act as specific transporters, as does serum retinol binding protein. <ref>PMID:15259212</ref> Bovine β-Lactoglobulin is synthesized in cow mammary gland and secreted in the milk. It causes an allergic reaction in human and is one of the causes of cow's milk allergy.

β-Lactoglobulin belongs to the calycin superfamily and Lipocalin family. Lipocalins are typically small (160-180 residues in length), extracellular proteins sharing several common molecular recognition properties: the binding of small, principally hydrophobic molecules (such as retinol); binding to specific cell-surface receptors; and the formation of covalent and non-covalent complexes with other soluble macromolecules. Although they have been classified mainly as transport proteins.  

β-Lactoglobulin contains two disulfide bonds (Cys 66–Cys 160 and Cys 106–Cys 119) and a free thiol (Cys 121)(Fig. 1). Structures of βLG have been reported by several groups with X-ray crystallography  and solution NMR It is a predominantly β-sheet protein. The β-barrel, or so called calyx, is conical and is made of two β-sheets: the B–D strands and N-terminal half of the A strand (denoted AN) form one sheet, and the E–H strands and C-terminal half of the A strand (denoted AC) form the other. On the outer surface of the β-barrel, between the G and H strands, is the 3-turn α-helix. The loops that connect the β-strands at the closed end of the calyx, BC, DE, and FG, are generally quite short, whereas those at the open end, AB, CD, EF,and GH, are significantly longer and more flexible. In the calyx, there is a large central cavity which is surrounded by hydrophobic residues and is accessible to solvent. This cavity provides the principal ligand-binding site (Fig. 2). <ref>PMID:19362581</ref>

The true function of β-Lg is unknown, but it has been suggested that it is involved in the transport of retinol and/or fatty acids. It binds retinol with a higher affinity than does RBP. β-Lg contains two tryptophans, Trp 19 on the A strand and Trp 61 on the C strand. The former is buried in the hydrophobic core whereas the latter is exposed to the solvent in the native structure, making them useful probes for monitoring site-specific conformational changes.<ref>PMID:19362581</ref> and their fluorescence is altered when retinol is bound <ref>PMID:9115437</ref>

Co-crystallized β-Lg with palmitic acid (3D Model 2._1B0O) , and the refined structure reveals that the ligand binds in the central cavity in a manner similar to the binding of retinol to the related lipocalin, serum retinol-binding protein. The carboxyl group binds to both Lys-60 and Lys-69 at the entrance to the cavity. The hydrophobic tail stretches in an almost fully extended conformation into the center of the protein.<ref>PMID:9867826</ref>

====Biological role====

β-LG interaction with hydrophobic molecules and with other proteins, and its sensitivity to chemical, thermal and baric denaturation, all with a view to establishing relationships among structure, properties and functionality and its potential use in food and pharmacy industry. <ref>http://www.sciencedirect.com/science/article/pii/S0958694698000211</ref>Food Industry has been widely utilize β-LG to increase functionality (sensory, texture, nutritional) in commercial food and beverages application, and also as cheap source of protein to increase the overall protein content of their product. Pharmacy Industry is recently investigating and developing design of drugs that utilize β-LG as vehicle to transport antioxidants, drugs and vitamins to the gut.<ref>http://www.faqs.org/patents/app/20110038942</ref>

In the dairy industry, bovine milk is frequently heated for pasteurization (62.5°C for 30 min) and sterilization. This heating process may induce oxidative losses of proteins, unsaturated lipids, vitamins, active enzymes, and immunological factors. Cross-linking the free thiol groups of β-LG by heating (100 °C for 2 min), or chemically modifying the β-LG by carboxymethylation to block the thiol groups resulted in a substantial loss of antioxidant activity. The data suggest that Cys-121 plays an essential role in the antioxidant nature of β-LG.Because β-LG is extremely sensitive to thermal denaturation, to maintain its antioxidant nature, dairy products consumed daily should not be overheated in order to maintain its antioxidant nature.<ref>PMID:17235131</ref>