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K-casein

From Wikipedia, the free encyclopedia

CSN3
Identifiers
AliasesCSN3, CSN10, CSNK, KCA, CNS10, casein kappa
External IDsOMIM: 601695; MGI: 107461; HomoloGene: 3818; GeneCards: CSN3; OMA:CSN3 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

1448

12994

Ensembl

ENSG00000171209

ENSMUSG00000001622

UniProt

P07498

P06796

RefSeq (mRNA)

NM_005212
NM_001394997

NM_007786
NM_001356570
NM_001356571

RefSeq (protein)

NP_005203

NP_031812
NP_001343499
NP_001343500

Location (UCSC)Chr 4: 70.24 – 70.25 MbChr 5: 88.07 – 88.08 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Κ-casein, or kappa casein, is a mammalian milk protein encoded in humans by the CSN3 gene.[5][6][7]

Structure

[edit]
Molecular surface model of K-Casein[8]

Caseins are a family of phosphoproteins (αS1, αS2, β, κ) that account for nearly 80% of bovine milk proteins.[9]

Caseins form soluble aggregates known as casein micelles, in which κ-casein contributes to micelle stabilization. Several models have been proposed to explain micellar organization.[10]

One model proposes that the micellar nucleus is formed from submicelles, with the periphery composed of κ-casein-rich microvillosities.[11][12]

Another model proposes a nucleus composed of casein-interlinked fibrils.[13] A later model proposes that gel formation depends on dual interactions among casein molecules.[14]

All three models describe micelles as colloidal particles composed of casein aggregates surrounded by soluble κ-casein molecules.

Function

[edit]

Κ-casein is involved in several important physiological processes in milk. Chymosin (found in rennet) cleaves κ-casein into an insoluble peptide, para-κ-casein, and a water-soluble glycomacropeptide (GMP).[15]

Milk-clotting proteases act on the soluble portion of κ-casein, generating an unstable micellar state that results in clot formation.[16]

Clinical significance

[edit]

Glycomacropeptide (GMP), generated by cleavage of κ-casein, has been reported to increase digestive efficiency, prevent neonate hypersensitivity to ingested proteins, and inhibit gastric pathogens.[15]

Applications

[edit]

Milk clotting

[edit]
In red/blue Phe105-Met106 bond of κ- casein[8]

Chymosin (EC 3.4.23.4) is an aspartic protease that specifically hydrolyzes the peptide bond in Phe105-Met106 of κ- casein and is considered to be the most efficient protease for the cheesemaking industry.[17] However, there are milk-clotting proteases able to cleave other peptide bonds in the κ-casein chain, such as the endothiapepsin produced by Endothia parasitica.[18] There are also several milk-clotting proteases that, being able to cleave the Phe105-Met106 bond in the κ-casein molecule, also cleave other peptide bonds in other caseins, such as those produced by Cynara cardunculus[12][19][20] or even bovine chymosin.[21] This allows the manufacture of different cheeses with a variety of rheological and organoleptic properties.

The milk-clotting process consists of three main phases:[22]

  1. Enzymatic degradation of κ-casein.
  2. Micellar flocculation.
  3. Gel formation.

Each step follows a different kinetic pattern, the limiting step in milk-clotting being the degradation rate of κ-casein. The kinetic pattern of the second step of the milk-clotting process is influenced by the cooperative nature of micellar flocculation,[23][20] whereas the rheological properties of the gel formed depend on the type of action of the proteases, the type of milk, and the patterns of casein proteolysis.[20] The overall process is influenced by several different factors, such as pH or temperature.[19][16]

The conventional way of quantifying a given milk-clotting enzyme[24] employs milk as the substrate and determines the time elapsed before the appearance of milk clots. However, milk clotting may take place without the participation of enzymes because of variations in physicochemical factors, such as low pH or high temperature.[12][9][16] Consequently, this may lead to confusing and irreproducible results, particularly when the enzymes have low activity. At the same time, the classical method is not specific enough, in terms of setting the precise onset of milk gelation, such that the determination of the enzymatic units involved becomes difficult and unclear. Furthermore, although it has been reported that κ-casein hydrolysis follows typical Michaelis–Menten kinetics,[22] it is difficult to determine with the classic milk-clotting assay.

To overcome this, several alternative methods have been proposed, such as the determination of halo diameter in agar-gelified milk,[24] colorimetric measurement,[25] or determination of the rate of degradation of casein previously labeled with either a radioactive tracer[26] or a fluorochrome compound.[27] All these methods use casein as the substrate to quantify proteolytic or milk-clotting activities.

Enzymatic assay

[edit]
Fluorescein isothiocyanate

Κ-casein labeled with the fluorochrome fluorescein isothiocyanate (FITC) to yield the fluorescein thiocarbamoyl (FTC) derivative. This substrate is used to determinate the milk clotting activity of proteases.[28]

FTC-κ-casein method affords accurate and precise determinations of κ-caseinolytic degradation, the first step in the milk-clotting process. This method is the result of a modification to the one described by S.S. Twining (1984). The main modification was substituting the substrate previously used (casein) by κ-casein labeled with the fluorochrome fluorescein isothiocyanate (FITC) to yield the fluorescein thiocarbamoyl (FTC) derivative. This variation allows quantification of the κ-casein molecules degraded in a more precise and specific way, detecting only those enzymes able to degrade such molecules. The method described by Twining (1984), however, was designed to detect the proteolytic activity of a considerably larger variety of enzymes. FTC-κ-casein allows the detection of different types of proteases at levels when no milk clotting is yet apparent, demonstrating its higher sensitivity over currently used assay procedures. Therefore, the method may find application as an indicator during the purification or characterization of new milk-clotting enzymes.

Interactions

[edit]

Kappa-casein has been shown to interact with EIF3S6.[29]

References

[edit]
  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000171209 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000001622 – 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. ↑ Edlund A, Johansson T, Leidvik B, Hansson L (November 1996). "Structure of the human kappa-casein gene". Gene. 174 (1): 65–69. doi:10.1016/0378-1119(96)00351-4. PMID 8863730.
  6. ↑ Fujiwara Y, Miwa M, Nogami M, Okumura K, Nobori T, Suzuki T, et al. (March 1997). "Genomic organization and chromosomal localization of the human casein gene family". Human Genetics. 99 (3): 368–373. doi:10.1007/s004390050374. PMID 9050925. S2CID 8299892.
  7. ↑ "Entrez Gene: CSN3 casein kappa".
  8. 1 2 Kumosinski TF, Brown EM, Farrell HM (September 1993). "Three-dimensional molecular modeling of bovine caseins: a refined, energy-minimized kappa-casein structure". Journal of Dairy Science. 76 (9): 2507–2520. doi:10.3168/jds.S0022-0302(93)77586-4. PMID 8227653.
  9. 1 2 Lucey JA, Johnson ME, Horne DS (September 2003). "Invited review: perspectives on the basis of the rheology and texture properties of cheese". Journal of Dairy Science. 86 (9): 2725–2743. doi:10.3168/jds.S0022-0302(03)73869-7. PMID 14507008.
  10. ↑ Dalgleish DG (1998). "Casein Micelles as Colloids: Surface Structures and Stabilities". Journal of Dairy Science. 81 (11): 3013–3018. doi:10.3168/jds.S0022-0302(98)75865-5.
  11. ↑ Walstra P (April 1979). "The voluminosity of bovine casein micelles and some of its implications". The Journal of Dairy Research. 46 (2): 317–323. doi:10.1017/S0022029900017234. PMID 469060. S2CID 222355860.
  12. 1 2 3 Lucey JA (2002). "Formation and Physical Properties of Milk Protein Gels". Journal of Dairy Science. 85 (2): 281–294. doi:10.3168/jds.S0022-0302(02)74078-2. PMID 11913691.
  13. ↑ Holt C (1992). "Structure and Stability of Bovine Casein Micelles". In Anfinsen CB, Richards FM, Edsall JT, et al. (eds.). Advances in Protein Chemistry Volume 43. Vol. 43. pp. 63–151. doi:10.1016/S0065-3233(08)60554-9. ISBN 978-0-12-034243-3. PMID 1442324.
  14. ↑ Horne DS (1998). "Casein Interactions: Casting Light on the Black Boxes, the Structure in Dairy Products". International Dairy Journal. 8 (3): 171–177. doi:10.1016/S0958-6946(98)00040-5.
  15. 1 2 "Kappa casein (IPR000117)". InterPro.
  16. 1 2 3 Vasbinder AJ, Rollema HS, Bot A, de Kruif CG (May 2003). "Gelation mechanism of milk as influenced by temperature and pH; studied by the use of transglutaminase cross-linked casein micelles". Journal of Dairy Science. 86 (5): 1556–1563. doi:10.3168/jds.S0022-0302(03)73741-2. PMID 12778566.
  17. ↑ Rao MB, Tanksale AM, Ghatge MS, Deshpande VV (September 1998). "Molecular and biotechnological aspects of microbial proteases". Microbiology and Molecular Biology Reviews. 62 (3): 597–635. doi:10.1128/MMBR.62.3.597-635.1998. PMC 98927. PMID 9729602.
  18. ↑ Drøhse HB, Foltmann B (May 1989). "Specificity of milk-clotting enzymes towards bovine kappa-casein". Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology. 995 (3): 221–224. doi:10.1016/0167-4838(89)90039-3. PMID 2495817.
  19. 1 2 Esteves CL, Lucey JA, Wang T, Pires EM (August 2003). "Effect of pH on the gelation properties of skim milk gels made from plant coagulants and chymosin". Journal of Dairy Science. 86 (8): 2558–2567. doi:10.3168/jds.S0022-0302(03)73850-8. hdl:10316/3878. PMID 12939079.
  20. 1 2 3 Silva SV, Malcata FX (June 2005). "Partial identification of water-soluble peptides released at early stages of proteolysis in sterilized ovine cheese-like systems: influence of type of coagulant and starter". Journal of Dairy Science. 88 (6): 1947–1954. doi:10.3168/jds.S0022-0302(05)72870-8. hdl:10400.14/6738. PMID 15905424.
  21. ↑ Kobayashi H (2004). "Polyporopepsin". In Barrett AJ, Woessner JF, Rawlings ND (eds.). Handbook of Proteolytic Enzymes. pp. 111–115. doi:10.1016/B978-0-12-079611-3.50035-5. ISBN 978-0-12-079611-3.
  22. 1 2 Carlson A, Hill CG, Olson NF (April 1987). "Kinetics of milk coagulation: I. The kinetics of kappa casein hydrolysis in the presence of enzyme deactivation". Biotechnology and Bioengineering. 29 (5): 582–589. Bibcode:1987BiotB..29..582C. doi:10.1002/bit.260290507. PMID 18576489. S2CID 38359395.
  23. ↑ Carlson A, Hill CG, Olson NF (April 1987). "Kinetics of milk coagulation: II. Kinetics of the secondary phase: micelle flocculation". Biotechnology and Bioengineering. 29 (5): 590–600. Bibcode:1987BiotB..29..590C. doi:10.1002/bit.260290508. PMID 18576490. S2CID 44397261.
  24. 1 2 Poza M, Sieiro C, Carreira L, Barros-Velázquez J, Villa TG (December 2003). "Production and characterization of the milk-clotting protease of Myxococcus xanthus strain 422". Journal of Industrial Microbiology & Biotechnology. 30 (12): 691–698. doi:10.1007/s10295-003-0100-y. PMID 14634834. S2CID 23067478.
  25. ↑ Hull ME (1947). "Studies on Milk Proteins. II. Colorimetric Determination of the Partial Hydrolysis of the Proteins in Milk". Journal of Dairy Science. 30 (11): 881–884. doi:10.3168/jds.S0022-0302(47)92412-0.
  26. ↑ Christen GL (September 1987). "A rapid method for measuring protease activity in milk using radiolabeled casein". Journal of Dairy Science. 70 (9): 1807–1814. doi:10.3168/jds.S0022-0302(87)80218-7. PMID 3117854.
  27. ↑ Twining SS (November 1984). "Fluorescein isothiocyanate-labeled casein assay for proteolytic enzymes". Analytical Biochemistry. 143 (1): 30–34. doi:10.1016/0003-2697(84)90553-0. PMID 6442109.
  28. ↑ Ageitos JM, Vallejo JA, Poza M, Villa TG (October 2006). "Fluorescein thiocarbamoyl-kappa-casein assay for the specific testing of milk-clotting proteases". Journal of Dairy Science. 89 (10): 3770–3777. doi:10.3168/jds.S0022-0302(06)72418-3. PMID 16960051.
  29. ↑ Hoareau Alves K, Bochard V, Réty S, Jalinot P (September 2002). "Association of the mammalian proto-oncoprotein Int-6 with the three protein complexes eIF3, COP9 signalosome and 26S proteasome". FEBS Letters. 527 (1–3): 15–21. doi:10.1016/S0014-5793(02)03147-2. PMID 12220626. S2CID 39308598.

Further reading

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