Alpha-lactalbumin

Lactalbumin, alpha-, also known as LALBA, is a protein that in humans is encoded by the LALBA gene.[5][6][7]

LALBA
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesLALBA, entrez:3906, LYZG, lactalbumin alpha
External IDsOMIM: 149750 MGI: 96742 HomoloGene: 1720 GeneCards: LALBA
Gene location (Human)
Chr.Chromosome 12 (human)[1]
Band12q13.11Start48,567,684 bp[1]
End48,570,066 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

3906

16770

Ensembl

ENSG00000167531

ENSMUSG00000022991

UniProt

P00709

P29752

RefSeq (mRNA)

NM_002289

NM_010679

RefSeq (protein)

NP_002280

NP_034809

Location (UCSC)Chr 12: 48.57 – 48.57 MbChr 15: 98.48 – 98.48 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

α-Lactalbumin is a protein that regulates the production of lactose in the milk of almost all mammalian species.[8] In primates, alpha-lactalbumin expression is upregulated in response to the hormone prolactin and increases the production of lactose.[9]

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.[5] The corresponding folding dynamics of alpha-lactalbumin is thus highly unusual.[10]

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

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

The sequence comparison of α-lactalbumin shows a strong similarity to that of lysozymes, specifically the Ca2+-binding c-lysozyme.[11] So the expected evolutionary history is that gene duplication of the c-lysozyme was followed by mutation.[8] This gene predates the last common ancestor of mammals and birds, which probably puts its origin at about 300 Ma.[12]

References

  1. GRCh38: Ensembl release 89: ENSG00000167531 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000022991 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: LALBA lactalbumin, alpha-".
  6. 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.
  7. 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. doi:10.1042/bj2420735. PMC 1147772. PMID 2954544.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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. S2CID 10039589.

Further reading

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