Arthropod defensin explained

Arthropod defensins are a family defensin proteins found in mollusks, insects, and arachnids. These cysteine-rich antibacterial peptides are primarily active against Gram-positive bacteria and fungi in vitro.[1] [2] [3] [4] [5] However Drosophila fruit flies mutant for the fly defensin were more susceptible to infection by the Gram-negative bacteria Providencia burhodogranariea, and resisted infection against Gram-positive bacteria like wild-type flies.[6] It remains to be seen how in vitro activity relates to in vivo function. Mutants for the defensin-like antimicrobial peptide Drosomycin were more susceptible to fungi, validating a role for defensin-like peptides in anti-fungal defence.[6]

Structure

Arthropod defensin peptides range in length from 38 to 51 amino acids. There are six conserved cysteines all involved in intrachain disulfide bonds. Studies have shown that the cysteine-bridge disulfide bonds are not required for antimicrobial activity,[7] similar to findings in mammalian defensins.[8] Furthermore, it was also shown that the N-terminal helix region in arthropod or insect defensins is also not required for antimicrobial activity of these peptides.

A schematic representation of peptides from the arthropod defensin family is shown below.

+----------------------------+ | | | | | | +---|---------------+ | +-----------------+'C': conserved cysteine involved in a disulfide bond.

Relation to other defensins

Sequence similarities have been reported between the arthropod defensins and mammalian defensins.[9] However it appears that defensins of vertebrates, arthropods, plants, and fungi arose independently.[10] This is supported by 3D structural differences between arthropod defensins and vertebrate beta defensins.[11] However structural similarities exist between these defensins, notably in two structural motifs termed "C6" and "C8". This has prompted a higher "cis-" or "tras-" defensin classification system wherein the structural relationships of the shared motifs is used to delineate defensin similarities.

Activity against non-microbial cells

Defensins of mammals display anti-cancer activities in vitro,[12] and down-regulation of human beta-defensin 1 is associated with increased risk of prostate cancer and clear-cell carcinomas.[13] The first in vivo anti-cancer functions for defensin came from Drosophila studies, which showed that the Drosophila defensin attacks tumor cells, and that flies lacking defensin had greater tumor growth in a cancer disease model.[14] [15]

Overactive immune signalling is also implicated in age-associated neurodegeneration,[16] and overexpression of defensin leads to increased degradation of brain tissue.[17]

Further reading

References

Notes and References

  1. Lambert J, Keppi E, Dimarcq JL, Wicker C, Reichhart JM, Dunbar B, Lepage P, Van Dorsselaer A, Hoffmann J, Fothergill J . 6 . Insect immunity: isolation from immune blood of the dipteran Phormia terranovae of two insect antibacterial peptides with sequence homology to rabbit lung macrophage bactericidal peptides . Proceedings of the National Academy of Sciences of the United States of America . 86 . 1 . 262–6 . January 1989 . 2911573 . 286444 . 10.1073/pnas.86.1.262 . 1989PNAS...86..262L . free .
  2. Fujiwara S, Imai J, Fujiwara M, Yaeshima T, Kawashima T, Kobayashi K . A potent antibacterial protein in royal jelly. Purification and determination of the primary structure of royalisin . The Journal of Biological Chemistry . 265 . 19 . 11333–7 . July 1990 . 10.1016/S0021-9258(19)38596-5 . 2358464 . free .
  3. Yamada K, Natori S . Purification, sequence and antibacterial activity of two novel sapecin homologues from Sarcophaga embryonic cells: similarity of sapecin B to charybdotoxin . The Biochemical Journal . 291 (Pt 1) . 275–9 . April 1993 . Pt 1 . 8471044 . 1132513 . 10.1042/bj2910275 .
  4. Bulet P, Cociancich S, Dimarcq JL, Lambert J, Reichhart JM, Hoffmann D, Hetru C, Hoffmann JA . 6 . Insect immunity. Isolation from a coleopteran insect of a novel inducible antibacterial peptide and of new members of the insect defensin family . The Journal of Biological Chemistry . 266 . 36 . 24520–5 . December 1991 . 10.1016/S0021-9258(18)54260-5 . 1761552 . free .
  5. Bulet P, Cociancich S, Reuland M, Sauber F, Bischoff R, Hegy G, Van Dorsselaer A, Hetru C, Hoffmann JA . 6 . A novel insect defensin mediates the inducible antibacterial activity in larvae of the dragonfly Aeschna cyanea (Paleoptera, Odonata) . European Journal of Biochemistry . 209 . 3 . 977–84 . November 1992 . 1425705 . 10.1111/j.1432-1033.1992.tb17371.x . free .
  6. Hanson MA, Dostálová A, Ceroni C, Poidevin M, Kondo S, Lemaitre B . Synergy and remarkable specificity of antimicrobial peptides in vivo using a systematic knockout approach . eLife . 8 . February 2019 . 30803481 . 6398976 . 10.7554/eLife.44341 . free .
  7. Varkey J, Singh S, Nagaraj R . Antibacterial activity of linear peptides spanning the carboxy-terminal beta-sheet domain of arthropod defensins . Peptides . 27 . 11 . 2614–23 . November 2006 . 16914230 . 10.1016/j.peptides.2006.06.010 . 21104756 .
  8. Varkey J, Nagaraj R . Antibacterial activity of human neutrophil defensin HNP-1 analogs without cysteines . Antimicrobial Agents and Chemotherapy . 49 . 11 . 4561–6 . November 2005 . 16251296 . 1280114 . 10.1128/AAC.49.11.4561-4566.2005 .
  9. Rosa RD, Santini A, Fievet J, Bulet P, Destoumieux-Garzón D, Bachère E . Big defensins, a diverse family of antimicrobial peptides that follows different patterns of expression in hemocytes of the oyster Crassostrea gigas . PLOS ONE . 6 . 9 . e25594 . 2011 . 21980497 . 3182236 . 10.1371/journal.pone.0025594 . 2011PLoSO...625594R . free .
  10. Shafee TM, Lay FT, Hulett MD, Anderson MA . The Defensins Consist of Two Independent, Convergent Protein Superfamilies . Molecular Biology and Evolution . 33 . 9 . 2345–56 . September 2016 . 27297472 . 10.1093/molbev/msw106 . free .
  11. Hanzawa H, Shimada I, Kuzuhara T, Komano H, Kohda D, Inagaki F, Natori S, Arata Y . 6 . 1H nuclear magnetic resonance study of the solution conformation of an antibacterial protein, sapecin . FEBS Letters . 269 . 2 . 413–20 . September 1990 . 2401368 . 10.1016/0014-5793(90)81206-4 . 30637946 . free .
  12. Deslouches B, Di YP . Antimicrobial peptides with selective antitumor mechanisms: prospect for anticancer applications . Oncotarget . 8 . 28 . 46635–46651 . July 2017 . 28422728 . 5542299 . 10.18632/oncotarget.16743 .
  13. Donald CD, Sun CQ, Lim SD, Macoska J, Cohen C, Amin MB, Young AN, Ganz TA, Marshall FF, Petros JA . Cancer-specific loss of beta-defensin 1 in renal and prostatic carcinomas . Laboratory Investigation; A Journal of Technical Methods and Pathology . 83 . 4 . 501–5 . April 2003 . 12695553 . 10.1097/01.LAB.0000063929.61760.F6. free .
  14. Parvy JP, Yu Y, Dostalova A, Kondo S, Kurjan A, Bulet P, Lemaitre B, Vidal M, Cordero JB . The antimicrobial peptide defensin cooperates with tumour necrosis factor to drive tumour cell death in Drosophila. . eLife . July 2019 . 8 . e45061 . 10.7554/eLife.45061 . 31358113 . 6667213 . free .
  15. Dawson KP, Abbott GD, Allan J . Acute respiratory infection in childhood: a study of parental prescribing patterns and advice sources . The New Zealand Medical Journal . 96 . 734 . 481–2 . June 1983 . 6602314 .
  16. Kounatidis I, Chtarbanova S, Cao Y, Hayne M, Jayanth D, Ganetzky B, Ligoxygakis P . NF-κB Immunity in the Brain Determines Fly Lifespan in Healthy Aging and Age-Related Neurodegeneration . Cell Reports . 19 . 4 . 836–848 . April 2017 . 28445733 . 5413584 . 10.1016/j.celrep.2017.04.007 .
  17. Cao Y, Chtarbanova S, Petersen AJ, Ganetzky B . Dnr1 mutations cause neurodegeneration in Drosophila by activating the innate immune response in the brain . Proceedings of the National Academy of Sciences of the United States of America . 110 . 19 . E1752–60 . May 2013 . 23613578 . 3651420 . 10.1073/pnas.1306220110. 2013PNAS..110E1752C . free .

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Arthropod defensin".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.