Alpha-lactalbumin

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Lactalbumin, alpha-

PDB rendering based on 1a4v.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols LALBA; MGC138521; MGC138523
External IDs OMIM: 149750 MGI: 96742 HomoloGene: 1720 GeneCards: LALBA Gene
EC number 2.4.1.22
RNA expression pattern
PBB GE LALBA 207816 at tn.png
More reference expression data
Orthologs
Species Human Mouse
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:
48.96 – 48.96 Mb		 Chr 15:
98.48 – 98.48 Mb
PubMed search [1] [2]
This box:

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

Contents

Function [edit]

α-Lactalbumin is an important whey protein in cow's milk (~1 g/l), and is also present in the milk of many other mammalian species. In primates, alpha-lactalbumin expression is upregulated in response to the hormone prolactin and increases the production of lactose.[4]

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]

Research by a Dr. Vincent Tuohy at the Cleveland Clinic is using α-Lactalbumin as the basis for a potential breast cancer vaccine.[citation needed] Breast cancer usually develops later in life, well after the typical child-bearing age. This protein is normally expressed only during late pregnancy and lactation, but Tuohy notes that expression is also common in newly formed tumours: “One of the things they do is make inappropriate proteins like α-lactalbumin". Dr. Tuohy's group has developed a vaccine that targets α-Lactalbumin, tricking the patient's own immune system to attack breast tissue that expresses the α-Lactalbumin genes and thus killing a high percentage of the cancerous cells. In fact, vaccinated mice achieved 100% protection against breast cancer, provided they were dosed before tumours began to develop. Tissue damage and inflammation were limited to the breast tissue of nursing animals. This should not be a problem for humans, as the highest risk breast cancer patients are generally past childbearing age.[5]

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 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.[6] So the expected evolutionary history is that gene duplication of the c-lysozyme was followed by mutation.[7] 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. ^ 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 97356016. 
  5. ^ Michael Eisenstein (2011). Nature 471 (7339): S8–S9. doi:10.1038/471S8a. 
  6. ^ 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. 
  7. ^ 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. 
  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]
Serum globulins
Other
Other globulins
Beta-lactoglobulin (Lactoferrin) · Thyroglobulin · Alpha-lactalbumin
Albumins
Other
C-reactive protein · Lactalbumin (Alpha-lactalbumin) · Parvalbumin · Ricin
Serum globulins
Other
Other globulins
Beta-lactoglobulin (Lactoferrin) · Thyroglobulin · Alpha-lactalbumin
Albumins
Other
C-reactive protein · Lactalbumin (Alpha-lactalbumin) · Parvalbumin · Ricin
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