Alpha-lactalbumin

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LALBA
Protein LALBA PDB 1a4v.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases LALBA, entrez:3906, LYZG, lactalbumin alpha
External IDs OMIM: 149750 MGI: 96742 HomoloGene: 1720 GeneCards: 3906
RNA expression pattern
PBB GE LALBA 207816 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_002289

NM_010679

RefSeq (protein)

NP_002280.1

NP_034809.1

Location (UCSC) Chr 12: 48.57 – 48.57 Mb Chr 15: 98.48 – 98.48 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

Lactalbumin, alpha-, also known as LALBA, is a protein that in humans is encoded by the LALBA gene.[1][2][3]

Function[edit]

α-Lactalbumin is a protein present in the milk of almost all mammalian species.[4] In primates, alpha-lactalbumin expression is upregulated in response to the hormone prolactin and increases the production of lactose.[5]

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.[1] The corresponding folding dynamics of alpha-lactalbumin is thus highly unusual.[6]

When formed into a complex with Gal-T1, a galactosyltransferase, α-lactalbumin, enhances the enzyme's affinity for glucose by about 1000 times, and inhibits the ability to polymerise multiple galactose units. This gives rise to a pathway for forming lactose by converting Gal-TI to Lactose synthase.

Physical properties[edit]

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.

Evolution[edit]

The sequence comparison of α-lactalbumin shows a strong similarity to that of lysozymes, specifically the Ca2+-binding c-lysozyme.[7] So the expected evolutionary history is that gene duplication of the c-lysozyme was followed by mutation.[4] This gene predates the last common ancestor of mammals and birds, which probably puts its origin at about 300 Ma.[8]

References[edit]

  1. ^ a b "Entrez Gene: LALBA lactalbumin, alpha-". 
  2. ^ Hall L, Davies MS, Craig RK (January 1981). "The construction, identification and characterisation of plasmids containing human alpha-lactalbumin cDNA sequences". Nucleic Acids Res. 9 (1): 65–84. doi:10.1093/nar/9.1.65. PMC 326669. PMID 6163135. 
  3. ^ Hall L, Emery DC, Davies MS, Parker D, Craig RK (March 1987). "Organization and sequence of the human alpha-lactalbumin gene". Biochem. J. 242 (3): 735–42. PMC 1147772. PMID 2954544. 
  4. ^ a b Qasba PK, Kumar S (1997). "Molecular divergence of lysozymes and alpha-lactalbumin". Crit. Rev. Biochem. Mol. Biol. 32 (4): 255–306. doi:10.3109/10409239709082574. PMID 9307874. 
  5. ^ Kleinberg JL, Todd J, Babitsky G (1983). "Inhibition by estradiol of the lactogenic effect of prolactin in primate mammary tissue: reversal by antiestrogens LY 156758 and tamoxifen.". PNAS 80 (13): 4144–4148. doi:10.1073/pnas.80.13.4144. PMC 394217. PMID 6575400. 
  6. ^ 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. PMID 11575938. 
  7. ^ 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. PMID 2769757. 
  8. ^ 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. PMID 3146643. 

Further reading[edit]

External links[edit]