Lactoferrin

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Lactoferrin
Lactoferrin
Belt model according to PDB  1B0L

Existing structure data: 1B0L , 1BKA , 1CB6 , 1DSN , 1EH3 , 1FCK , 1H43 , 1H44 , 1h45 , 1HSE , 1L5T , 1LCF , 1LCT , 1LFG , 1LFH , 1LFI , 1LGB , 1N76 , 1SQY , 1U62 , 1VFD , 1VFE , 1XV4 , 1XV7 , 1Z6V , 1Z6W , 2BJJ , 2DP4 , 2GMC , 2GMD , 2HD4 , 2PMS

Properties of human protein
Mass / length primary structure 691 amino acids
Identifier
Gene names LTF GIG12; HEL110; HLF2; LF
External IDs
Enzyme classification
EC, category 3.4.21. ,  Serine protease
MEROPS S60.001
Response type Cleavage of a peptide bond
Substrate X-Arg-Ser-Arg-Arg - * - Y or X-Arg-Arg-Ser-Arg - * - Y
Products Y + X-Arg-Ser-Arg-Arg or X-Arg-Arg-Ser-Arg
Occurrence
Homology family Transferrin
Parent taxon Euteleostomi
Orthologue
human House mouse
Entrez 4057 17002
Ensemble ENSG00000012223 ENSMUSG00000032496
UniProt P02788 P08071
Refseq (mRNA) NM_001199149 NM_008522
Refseq (protein) NP_001186078 NP_032548
Gene locus Chr 3: 46.44 - 46.49 Mb Chr 9: 111.02 - 111.04 Mb
PubMed search 4057 17002

Lactoferrin (more precisely: lactotransferrin , from Latin lacteus 'milk' and Latin ferrum 'iron' and Latin transferre ' transfer ') is a protein found in mammals with multifunctional enzyme activities .

evolution

Lactoferrin belongs to the transferrins protein family . Transferrins are not only found in mammals, homologous genes are also found in other vertebrates and invertebrates.

Properties and occurrence

Lactoferrin has both antiviral and antimicrobial properties. On the one hand, it functions as a peptidase (cleavage of peptides ), which is why it is assigned to the group of serine proteases , but also as an iron- binding protein - similar to transferrin - and also shows deoxyribonuclease and ribonuclease activities, which means that it is classified as nucleases ( EC  3.1. 21.1 ) is added. It is also a powerful inhibitor of tryptase .

Lactoferrin is found in many body fluids of mammals, in their milk , tears , saliva , sweat , vaginal secretions , seminal plasma , nasal and bronchial secretions as well as other secretions . It is also localized in white blood cells .

Even small amounts develop enormous biological activity. One liter of cow's milk contains 0.1 g of lactoferrin. It is only slightly saturated with iron and can bind more than five times its original iron charge.

It also influences cell division and stimulates cell growth. It also exerts immunological effects by promoting the growth of lymphocytes.

Antibacterial protective function

Lactoferrin is used by the body to remove the iron that is essential for life from bacteria. Since bacteria are essentially dependent on iron, iron depletion has an antibacterial effect. As a protease, lactoferrin is able to destroy several proteins of the Haemophilus influenzae pathogen that are important for colonization . In particular, the concentration of lactoferrin found in human breast milk can prevent the respiratory tract infections with this germ , which often occur in small children . It also affects the type III secretion system in Shigella and pathogenic Escherichia coli . Released by leukocytes, it is part of the immune system .

Viral interactions

Infections with HTLV-1 via breast milk or seminal plasma are favored by lactoferrin. On the other hand, the protein can prevent the replication of HIV- 1.

use

Several studies at the beginning of the 21st century show remarkable results in the treatment of chronic periodontal disease .

The pharmaceutical industry is interested in this protein because of its broad spectrum of activity. Industrially, it is isolated from milk and whey. It is used in baby and sports nutrition, as well as in cosmetics, chewing gum and functional foods .

As a study by the Journal of the American Medical Association from 2009 showed, the administration of lactoferrin to newborns who are underweight (<1500 g birth weight) can significantly and clinically relevantly reduce the incidence of sepsis and sepsis-associated mortality.

literature

Individual evidence

  1. ^ Ward PP, Paz E, Conneely OM: Multifunctional roles of lactoferrin: a critical overview . In: Cell. Mol. Life Sci. . 62, No. 22, November 2005, pp. 2540-8. doi : 10.1007 / s00018-005-5369-8 . PMID 16261256 .
  2. ^ A b John Williams: The evolution of transferrin. In: Trends in Biochemical Sciences. 7, 1982, pp. 394-397, doi : 10.1016 / 0968-0004 (82) 90183-9 .
  3. ↑ Guo Ming Liang, Xun Ping Jiang: Positive selection drives lactoferrin evolution in mammals. In: Genetica. 138, 2010, pp. 757-762, doi : 10.1007 / s10709-010-9456-x .
  4. ↑ Ciuraszkiewicz, Justyna et al .: Reptilian transferrins: evolution of disulphide bridges and conservation of iron-binding center. Gene, Volume 396, No. 1, 2007, pp. 28-38, doi : 10.1016 / j.gene.2007.02.018
  5. ↑ MC Harmsen, et al .: Antiviral Effects of Plasma and Milk Proteins: Lactoferrin Shows Potent Activity against Both Human Immunodeficiency Virus and Human Cytomegalovirus Replication In Vitro. In: Journal of Infectious Diseases. 172, 1995, pp. 380-388, doi : 10.1093 / infdis / 172.2.380 .
  6. ↑ a b c d e J. H. Park, GT Park, IH Cho, SM Sim, JM Yang, DY Lee: An antimicrobial protein, lactoferrin exists in the sweat: proteomic analysis of sweat. In: Experimental Dermatology . Volume 20, Number 4, April 2011, ISSN  1600-0625 , pp. 369-371, doi : 10.1111 / j.1600-0625.2010.01218.x , PMID 21366701
  7. ↑ Bennett, RM, J. Davis: Lactoferrin interacts with deoxyribonucleic acid: a preferential reactivity with double-stranded DNA and dissociation of DNA-anti-DNA complexes. The Journal of Laboratory and Clinical Medicine, Vol. 99, No. 1, 1982, p. 127, PMID 6274982 .
  8. ↑ Furmanski, Philip, et al .: Multiple molecular forms of human lactoferrin. Identification of a class of lactoferrins that possess ribonuclease activity and lack iron binding capacity. In: Journal of Experimental Medicine. 170, 1989, pp. 415-429, doi : 10.1084 / jem.170.2.415 .
  9. ↑ a b Elrod, Kyle C., et al .: Lactoferrin, a Potent Tryptase Inhibitor, Abolishes Late-Phase Airway Responses in Allergic Sheep. In: American Journal of Respiratory and Critical Care Medicine. 156, 1997, pp. 375-381, doi : 10.1164 / ajrccm.156.2.9607012 .
  10. ↑ PL Masson, JF Heremans, CH Dive: An iron-binding protein common to many external secretions. In: Clinica Chimica Acta. 14, 1966, pp. 735-739, doi : 10.1016 / 0009-8981 (66) 90004-0 .
  11. ^ Neville, Margaret C. et al .: Lactoferrin secretion into mouse milk. Advances in Lactoferrin Research. Plenum Press, New York (1998), pp. 141-153.
  12. ↑ Neville, MC, P. Zhang: Lactoferrin secretion into milk: comparison between ruminant, murine, and human milk.  ( Page no longer available , search in web archives )  Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice. (PDF; 1.4 MB)@1@ 2Template: Dead Link / www.animal-science.org   Journal of Animal Science, Volume 78, Suppl 3, 2000, pp. 26-35.
  13. ↑ Cohen, MS et al .: Preliminary observations on lactoferrin secretion in human vaginal mucus: variation during the menstrual cycle, evidence of hormonal regulation, and implications for infection with Neisseria gonorrhoeae. American Journal of Obstetrics and Gynecology, Vol. 157, No. 5, 1987, pp. 1122-1125.
  14. ↑ World Cup Buckett, MJ Luckas, MR Gazvani, IA Aird, DI Lewis-Jones: Seminal plasma lactoferrin Concentrations in normal and abnormal semen samples. In: Journal of andrology. Volume 18, Number 3, 1997 May-Jun, ISSN  0196-3635 , pp. 302-304, PMID 9203059 .
  15. ^ Legrand D, Pierce A, Elass E, Carpentier M, Mariller C, Mazurier J: Lactoferrin structure and functions . In: ... Adv Exp Med Biol. . 606, 2008, pp. 163-94. PMID 18183929 .
  16. ↑ Anderson BF, Baker HM, Dodson EJ, et al : Structure of human lactoferrin at 3.2-A resolution . In: Proc. Natl. Acad. Sci. USA . 84, No. 7, April 1987, pp. 1769-73. PMID 3470756 . PMC 304522 (free full text).
  17. ↑ Andrew G Plaut, Jiazhou Qiu, Joseph W St. Geme: Human lactoferrin proteolytic activity: analysis of the cleaved region in the IgA protease of Haemophilus influenzae. In: Vaccine. 19, 2000, pp. S148-S152, doi : 10.1016 / S0264-410X (00) 00296-6 .
  18. ↑ Qiu J, Hendrixson DR, Baker EN, Murphy TF, St Geme JW, Plaut AG: Human milk lactoferrin inactivates two putative colonization factors expressed by Haemophilus influenzae . In: Proc. Natl. Acad. Sci. USA . 95, No. 21, October 1998, pp. 12641-6. PMID 9770539 . PMC 22884 (free full text).
  19. ↑ Hendrixson DR, Qiu J, Shewry SC, et al : Human milk lactoferrin is a serine protease that cleaves Haemophilus surface proteins at arginine-rich sites . In: Mol. Microbiol. . 47, No. 3, February 2003, pp. 607-17. PMID 12535064 .
  20. ↑ Ochoa TJ, Clearly TG: Lactoferrin disruption of bacterial type III secretion systems . In: Biometals . 17, No. 3, June 2004, pp. 257-60. PMID 15222474 .
  21. ↑ Moriuchi, Masako, and Hiroyuki Moriuchi: Induction of lactoferrin gene expression in myeloid or mammary gland cells by human T-cell leukemia virus type 1 (HTLV-1) tax: implications for milk-borne transmission of HTLV-1. Journal of Virology, Vol. 80, No. 14, 2006, pp. 7118-7126.
  22. ↑ Moriuchi, Masako, Hiroyuki Moriuchi: Seminal fluid enhances replication of human T-cell leukemia virus type 1: implications for sexual transmission. Journal of Virology, Vol. 78, No. 22, 2004, pp. 12709-12711.
  23. ↑ Moriuchi M, Moriuchi H: A milk protein lactoferrin enhances human T cell leukemia virus type I and suppresses HIV-1 infection . In: J. Immunol. . 166, No. 6, March 2001, pp. 4231-6. PMID 11238676 .
  24. ↑ F. Berlutti, A. Pilloni et al. a .: Lactoferrin and oral diseases: current status and perspective in periodontitis. In: Annali di stomatologia. Volume 2, number 3-4, March 2011, ISSN  1824-0852 , pp. 10-18, PMID 22545184 , PMC 3314318 (free full text).
  25. ↑ Manzoni P, Rinaldi M, Cattani S, et al. : Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial . In: JAMA . 302, No. 13, October 2009, pp. 1421-1428. doi : 10.1001 / jama.2009.1403 . PMID 19809023 .