Cathelicidin
| Cathelicidin | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 Crystal Structure Analysis of the Cathelicidin Motif of Protegrins | |||||||||
| Identifiers | |||||||||
| Symbol | Cathelicidin | ||||||||
| Pfam | PF00666 | ||||||||
| Pfam clan | CL0121 | ||||||||
| InterPro | IPR001894 | ||||||||
| PROSITE | PDOC00729 | ||||||||
| SCOP | 1lyp | ||||||||
| SUPERFAMILY | 1lyp | ||||||||
| OPM superfamily | 236 | ||||||||
| OPM protein | 2k6o | ||||||||
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Cathelicidin-related antimicrobial peptides are a family of polypeptides found in lysosomes of macrophages and polymorphonuclear leukocytes (PMNs).[1] Cathelicidins serve a critical role in mammalian innate immune defense against invasive bacterial infection.[2]
Members of the cathelicidin family of antimicrobial polypeptides are characterized by a highly conserved region (cathelin domain) and a highly variable cathelicidin peptide domain.[3]
Cathelicidin peptides have been isolated from many different species of mammals. Cathelicidins were originally found in neutrophils but have since been found in many other cells including epithelial cells and macrophages after activation by bacteria, viruses, fungi, or the hormone 1,25-D, which is the hormonally active form of vitamin D.[4]
The cathelicidin family shares primary sequence homology with the cystatin[5] family of cysteine proteinase inhibitors, although amino acid residues thought to be important in such protease inhibition are usually lacking.
Characteristics
Cathelicidins range in size from 12 to 80 amino acid residues and have a wide range of structures.[6] Most cathelicidins are linear peptides with 23-37 amino acid residues, and fold into amphiphatic α-helices. Additionally cathelicidins may also be small-sized molecules (12-18 residues) with beta-hairpin structures, stabilized by one or two disulphide bonds. Even larger cathelicidin peptides (39-80 amino acid residues) are also present. These larger cathelicidins display repetitive proline motifs forming extended polyproline-type structures.[3]
Family members
Cathelicidin family components have been found in: humans, monkeys, mice, rats, rabbits, guinea pigs, pandas, pigs, cattle, frogs, sheep, goats, and horses.
Currently identified cathelicidins include the following:[3]
- Human:hCAP-18/LL-37
- Rhesus Monkey: RL-37
- Mice:CRAMP-1/2, (Cathelicidin-related Antimicrobial Peptide[7]
- Rats: rCRAMP
- Rabbits: CAP-18
- Guinea Pig: CAP-11
- Pigs: PR-39, Prophenin, PMAP-23,36,37
- Cattle: BMAP-27,28,34 (Bovine Myeloid Antimicrobial Peptides); Bac5, Bac7
- Frogs: cathelicidin-AL (found in Amolops loloensis)[8]
- Sheep:
- Goats:
- Horses:
- Pandas:
Clinical significance
Patients with rosacea have elevated levels of cathelicidin and elevated levels of stratum corneum tryptic enzymes (SCTEs). Antibiotics have been used in the past to treat rosacea, but antibiotics may only work because they inhibit some SCTEs.[9]
Higher levels of human cathelicidin antimicrobial protein (hCAP18), which are up-regulated by vitamin D, appear to significantly reduce the risk of death from infection in dialysis patients. Patients with a high level of this protein were 3.7 times more likely to survive kidney dialysis for a year without a fatal infection.[10]
Vitamin D up-regulates genetic expression of cathelicidin, which exhibits broad-spectrum microbicidal activity against bacteria, fungi, and viruses.[11][12] Cathelicidin rapidly destroys the lipoprotein membranes of microbes enveloped in phagosomes after fusion with lysosomes in macrophages.
See also
References
- ↑ "Entrez Gene: CAMP cathelicidin antimicrobial peptide".
- ↑ Nizet V, Ohtake T, Lauth X, Trowbridge J, Rudisill J, Dorschner RA, Pestonjamasp V, Piraino J, Huttner K, Gallo RL (November 2001). "Innate antimicrobial peptide protects the skin from invasive bacterial infection". Nature 414 (6862): 454–7. doi:10.1038/35106587. PMID 11719807.
- ↑ 3.0 3.1 3.2 Zanetti M (January 2004). "Cathelicidins, multifunctional peptides of the innate immunity". J. Leukoc. Biol. 75 (1): 39–48. doi:10.1189/jlb.0403147. PMID 12960280.
- ↑ Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, Ochoa MT, Schauber J, Wu K, Meinken C, Kamen DL, Wagner M, Bals R, Steinmeyer A, Zügel U, Gallo RL, Eisenberg D, Hewison M, Hollis BW, Adams JS, Bloom BR, Modlin R (March 2006). "Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response". Science 311 (5768): 1770–3. doi:10.1126/science.1123933. PMID 16497887.
- ↑ Zaiou M, Nizet V, Gallo RL. (May 2003). "Antimicrobial and protease inhibitory functions of the human cathelicidin (hCAP18/LL-37) prosequence". J Invest Dermatol. 5 (120): 810–6. doi:10.1046/j.1523-1747.2003.12132.x3. PMID 12713586.
- ↑ Gennaro R, Zanetti M (2000). "Structural features and biological activities of the cathelicidin-derived antimicrobial peptides". Biopolymers 55 (1): 31–49. doi:10.1002/1097-0282(2000)55:1<31::AID-BIP40>3.0.CO;2-9. PMID 10931440.
- ↑ Gallo RL, Kim KJ, Bernfield M, Kozak CA, Zanetti M, Merluzzi L, Gennaro R (May 1997). "Identification of CRAMP, a cathelin-related antimicrobial peptide expressed in the embryonic and adult mouse". J. Biol. Chem. 272 (20): 13088–93. doi:10.1074/jbc.272.20.13088. PMID 9148921.
- ↑ Hao X, Yang H, Wei L, Yang S, Zhu W, Ma D, Yu H, Lai R (August 2012). "Amphibian cathelicidin fills the evolutionary gap of cathelicidin in vertebrate". Amino Acids 43 (2): 677–85. doi:10.1007/s00726-011-1116-7. PMID 22009138.
- ↑ Yamasaki K, Di Nardo A, Bardan A, Murakami M, Ohtake T, Coda A, Dorschner RA, Bonnart C, Descargues P, Hovnanian A, Morhenn VB, Gallo RL (August 2007). "Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea". Nat. Med. 13 (8): 975–80. doi:10.1038/nm1616. PMID 17676051.
- ↑ Gombart AF, Bhan I, Borregaard N, Tamez H, Camargo CA, Koeffler HP, Thadhani R (February 2009). "Low plasma level of cathelicidin antimicrobial peptide (hCAP18) predicts increased infectious disease mortality in patients undergoing hemodialysis". Clin. Infect. Dis. 48 (4): 418–24. doi:10.1086/596314. PMID 19133797.
- ↑ Zasloff M (January 2002). "Antimicrobial peptides of multicellular organisms". Nature 415 (6870): 389–95. doi:10.1038/415389a. PMID 11807545.
- ↑ Kamen DL, Tangpricha V (May 2010). "Vitamin D and molecular actions on the immune system: modulation of innate and autoimmunity". J. Mol. Med. 88 (5): 441–50. doi:10.1007/s00109-010-0590-9. PMC 2861286. PMID 20119827.
Further reading
- Dürr UH, Sudheendra US, Ramamoorthy A (September 2006). "LL-37, the only human member of the cathelicidin family of antimicrobial peptides". Biochim. Biophys. Acta 1758 (9): 1408–25. doi:10.1016/j.bbamem.2006.03.030. PMID 16716248.
- Chromek M, Slamová Z, Bergman P, Kovács L, Podracká L, Ehrén I, Hökfelt T, Gudmundsson GH, Gallo RL, Agerberth B, Brauner A (June 2006). "The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection". Nat. Med. 12 (6): 636–41. doi:10.1038/nm1407. PMID 16751768.
- Gombart AF, Borregaard N, Koeffler HP (July 2005). "Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3". FASEB J. 19 (9): 1067–77. doi:10.1096/fj.04-3284com. PMID 15985530.
- López-García B, Lee PH, Gallo RL (May 2006). "Expression and potential function of cathelicidin antimicrobial peptides in dermatophytosis and tinea versicolor". J. Antimicrob. Chemother. 57 (5): 877–82. doi:10.1093/jac/dkl078. PMID 16556635.
- Lehrer RI, Ganz T (2002). "Cathelicidins: a family of endogenous antimicrobial peptides". Curr. Opin. Hematol. 9 (1): 18–22. doi:10.1097/00062752-200201000-00004. PMID 11753073.
- Niyonsaba F, Hirata M, Ogawa H, Nagaoka I (2003). "Epithelial cell-derived antibacterial peptides human beta-defensins and cathelicidin: multifunctional activities on mast cells". Current drug targets. Inflammation and allergy 2 (3): 224–31. doi:10.2174/1568010033484115. PMID 14561157.
- van Wetering S, Tjabringa GS, Hiemstra PS (2005). "Interactions between neutrophil-derived antimicrobial peptides and airway epithelial cells". J. Leukoc. Biol. 77 (4): 444–50. doi:10.1189/jlb.0604367. PMID 15591123.
- Agerberth B, Gunne H, Odeberg J, et al. (1995). "FALL-39, a putative human peptide antibiotic, is cysteine-free and expressed in bone marrow and testis". Proc. Natl. Acad. Sci. U.S.A. 92 (1): 195–9. doi:10.1073/pnas.92.1.195. PMC 42844. PMID 7529412.
- Cowland JB, Johnsen AH, Borregaard N (1995). "hCAP-18, a cathelin/pro-bactenecin-like protein of human neutrophil specific granules". FEBS Lett. 368 (1): 173–6. doi:10.1016/0014-5793(95)00634-L. PMID 7615076.
- Gudmundsson GH, Magnusson KP, Chowdhary BP, et al. (1995). "Structure of the gene for porcine peptide antibiotic PR-39, a cathelin gene family member: comparative mapping of the locus for the human peptide antibiotic FALL-39". Proc. Natl. Acad. Sci. U.S.A. 92 (15): 7085–9. doi:10.1073/pnas.92.15.7085. PMC 41476. PMID 7624374.
- Larrick JW, Hirata M, Balint RF, et al. (1995). "Human CAP18: a novel antimicrobial lipopolysaccharide-binding protein". Infect. Immun. 63 (4): 1291–7. PMC 173149. PMID 7890387.
- Gudmundsson GH, Agerberth B, Odeberg J, et al. (1996). "The human gene FALL39 and processing of the cathelin precursor to the antibacterial peptide LL-37 in granulocytes". Eur. J. Biochem. 238 (2): 325–32. doi:10.1111/j.1432-1033.1996.0325z.x. PMID 8681941.
- Larrick JW, Lee J, Ma S, et al. (1997). "Structural, functional analysis and localization of the human CAP18 gene". FEBS Lett. 398 (1): 74–80. doi:10.1016/S0014-5793(96)01199-4. PMID 8946956.
- Frohm M, Agerberth B, Ahangari G, et al. (1997). "The expression of the gene coding for the antibacterial peptide LL-37 is induced in human keratinocytes during inflammatory disorders". J. Biol. Chem. 272 (24): 15258–63. doi:10.1074/jbc.272.24.15258. PMID 9182550.
- Bals R, Wang X, Zasloff M, Wilson JM (1998). "The peptide antibiotic LL-37/hCAP-18 is expressed in epithelia of the human lung where it has broad antimicrobial activity at the airway surface". Proc. Natl. Acad. Sci. U.S.A. 95 (16): 9541–6. doi:10.1073/pnas.95.16.9541. PMC 21374. PMID 9689116.
- De Yang , Chen Q, Schmidt AP, et al. (2000). "LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells". J. Exp. Med. 192 (7): 1069–74. doi:10.1084/jem.192.7.1069. PMC 2193321. PMID 11015447.
- Agerberth B, Charo J, Werr J, et al. (2000). "The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins are expressed by specific lymphocyte and monocyte populations". Blood 96 (9): 3086–93. PMID 11049988.
- Bals R, Lang C, Weiner DJ, et al. (2001). "Rhesus monkey (Macaca mulatta) mucosal antimicrobial peptides are close homologues of human molecules". Clin. Diagn. Lab. Immunol. 8 (2): 370–5. doi:10.1128/CDLI.8.2.370-375.2001. PMC 96065. PMID 11238224.
- Nagaoka I, Hirota S, Niyonsaba F, et al. (2001). "Cathelicidin family of antibacterial peptides CAP18 and CAP11 inhibit the expression of TNF-alpha by blocking the binding of LPS to CD14(+) cells". J. Immunol. 167 (6): 3329–38. PMID 11544322.
- Hase K, Eckmann L, Leopard JD, et al. (2002). "Cell differentiation is a key determinant of cathelicidin LL-37/human cationic antimicrobial protein 18 expression by human colon epithelium". Infect. Immun. 70 (2): 953–63. doi:10.1128/IAI.70.2.953-963.2002. PMC 127717. PMID 11796631.
- Giuliani A, Pirri G, Nicoletto S (2007). "Antimicrobial peptides: an overview of a promising class of therapeutics". Cent. Eur. J. Biol. 2 (1): 1–33. doi:10.2478/s11535-007-0010-5.
- Burton MF, Steel PG (2009). "Chemistry and Biology of LL-37". Natural Product Reports, 26 (12): 1572–1584. doi:10.1039/b912533g.
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