α-Lactalbumin is a protein present in the milk of almost all mammalian species. In primates, alpha-lactalbumin expression is upregulated in response to the hormone prolactin and increases the production of lactose.
α-Lactalbumin forms the regulatory subunit of the lactose synthase (LS) heterodimer and β-1,4-galactosyltransferase (beta4Gal-T1) forms the catalytic component. Together, these proteins enable LS to produce lactose by transferring galactose moieties to glucose. As a multimer, alpha-lactalbumin strongly binds calcium and zinc ions and may possess bactericidal or antitumor activity. A folding variant of human alpha-lactalbumin that may form in acidic environments such as the stomach, called HAMLET, probably induces apoptosis in tumor and immature cells. The corresponding folding dynamics of alpha-lactalbumin is thus highly unusual.
The structure of alpha-lactalbumin is well known and is composed of 123 amino acids and 4 disulfide bridges. The molecular weight is 14178 Da, and the isoelectric point is between 4.2 and 4.5. One of the main structural differences with beta-lactoglobulin is that it does not have any free thiol group that can serve as the starting-point for a covalent aggregation reaction. As a result, pure α-lactalbumin will not form gels upon denaturation and acidification.
The sequence comparison of α-lactalbumin shows a strong similarity to that of lysozymes, specifically the Ca2+-binding c-lysozyme. So the expected evolutionary history is that gene duplication of the c-lysozyme was followed by mutation. This gene predates the last common ancestor of mammals and birds, which probably puts its origin at about 300 Ma.
^Bu, Z., Cook, J., Callaway, D. J. E. (2001). "Dynamic regimes and correlated structural dynamics in native and denatured alpha-lactalbumin". J. Mol. Biol.312 (4): 865–873. doi:10.1006/jmbi.2001.5006. PMID11575938.
^Acharya KR, Stuart DI, Walker NP, Lewis M, Phillips DC (1989). "Refined structure of baboon alpha-lactalbumin at 1.7 A resolution. Comparison with C-type lysozyme". J. Mol. Biol.208 (1): 99–127. doi:10.1016/0022-2836(89)90091-0. PMID2769757.
^Prager EM, Wilson AC (1988). "Ancient origin of lactalbumin from lysozyme: analysis of DNA and amino acid sequences". J. Mol. Evol.27 (4): 326–35. doi:10.1007/BF02101195. PMID3146643.
Lindner RA, Kapur A, Carver JA (1997). "The interaction of the molecular chaperone, alpha-crystallin, with molten globule states of bovine alpha-lactalbumin.". J. Biol. Chem.272 (44): 27722–9. doi:10.1074/jbc.272.44.27722. PMID9346914.
Giuffrida MG, Cavaletto M, Giunta C et al. (1998). "The unusual amino acid triplet Asn-Ile-Cys is a glycosylation consensus site in human alpha-lactalbumin.". J. Protein Chem.16 (8): 747–53. doi:10.1023/A:1026359715821. PMID9365923.
Chandra N, Brew K, Acharya KR (1998). "Structural evidence for the presence of a secondary calcium binding site in human alpha-lactalbumin.". Biochemistry37 (14): 4767–4772. doi:10.1021/bi973000t. PMID9537992.
Håkansson A, Andréasson J, Zhivotovsky B et al. (1999). "Multimeric alpha-lactalbumin from human milk induces apoptosis through a direct effect on cell nuclei.". Exp. Cell Res.246 (2): 451–60. doi:10.1006/excr.1998.4265. PMID9925761.
Svensson M, Sabharwal H, Håkansson A et al. (1999). "Molecular characterization of alpha-lactalbumin folding variants that induce apoptosis in tumor cells.". J. Biol. Chem.274 (10): 6388–6396. doi:10.1074/jbc.274.10.6388. PMID10037730.
Harata K, Abe Y, Muraki M (1999). "Crystallographic evaluation of internal motion of human alpha-lactalbumin refined by full-matrix least-squares method.". J. Mol. Biol.287 (2): 347–58. doi:10.1006/jmbi.1999.2598. PMID10080897.
Last AM, Schulman BA, Robinson CV, Redfield C (2001). "Probing subtle differences in the hydrogen exchange behavior of variants of the human alpha-lactalbumin molten globule using mass spectrometry.". J. Mol. Biol.311 (4): 909–19. doi:10.1006/jmbi.2001.4911. PMID11518539.
Andrews P (1970). "Purification of lactose synthetase a protein from human milk and demonstration of its interaction with alpha-lactalbumin.". FEBS Letters9 (5): 297–300. doi:10.1016/0014-5793(70)80382-9. PMID11947697.