{{Pfam box | Symbol = Defensin_2 | Name = Arthropod defensin | image = PDB_1ica_EBI.jpg | width = | caption = Structure of insect defensin A.<ref name="pmid7663941">{{cite journal | vauthors = Cornet B, Bonmatin JM, Hetru C, Hoffmann JA, Ptak M, Vovelle F | title = Refined three-dimensional solution structure of insect defensin A | journal = Structure | volume = 3 | issue = 5 | pages = 435–48 | date = May 1995 | pmid = 7663941 | doi = 10.1016/S0969-2126(01)00177-0 | doi-access = free }}</ref> | Pfam= PF01097 | InterPro= IPR001542 | SMART= | PROSITE = PDOC00356 | SCOP = 1ica | TCDB = 1.C.47 | OPM family= 58 | OPM protein= 1l4v }}
'''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.<ref name="Lambert_1989">{{cite journal | vauthors = Lambert J, Keppi E, Dimarcq JL, Wicker C, Reichhart JM, Dunbar B, Lepage P, Van Dorsselaer A, Hoffmann J, Fothergill J | display-authors = 6 | title = 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 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 86 | issue = 1 | pages = 262–6 | date = January 1989 | pmid = 2911573 | pmc = 286444 | doi = 10.1073/pnas.86.1.262 | bibcode = 1989PNAS...86..262L | doi-access = free }}</ref><ref name="PUB00002559">{{cite journal | vauthors = Fujiwara S, Imai J, Fujiwara M, Yaeshima T, Kawashima T, Kobayashi K | title = A potent antibacterial protein in royal jelly. Purification and determination of the primary structure of royalisin | journal = The Journal of Biological Chemistry | volume = 265 | issue = 19 | pages = 11333–7 | date = July 1990 | doi = 10.1016/S0021-9258(19)38596-5 | pmid = 2358464 | doi-access = free }}</ref><ref name="PUB00000525">{{cite journal | vauthors = Yamada K, Natori S | title = Purification, sequence and antibacterial activity of two novel sapecin homologues from Sarcophaga embryonic cells: similarity of sapecin B to charybdotoxin | journal = The Biochemical Journal | volume = 291 ( Pt 1) | pages = 275–9 | date = April 1993 | issue = Pt 1 | pmid = 8471044 | pmc = 1132513 | doi = 10.1042/bj2910275 }}</ref><ref name="PUB00002677">{{cite journal | vauthors = Bulet P, Cociancich S, Dimarcq JL, Lambert J, Reichhart JM, Hoffmann D, Hetru C, Hoffmann JA | display-authors = 6 | title = Insect immunity. Isolation from a coleopteran insect of a novel inducible antibacterial peptide and of new members of the insect defensin family | journal = The Journal of Biological Chemistry | volume = 266 | issue = 36 | pages = 24520–5 | date = December 1991 | doi = 10.1016/S0021-9258(18)54260-5 | pmid = 1761552 | doi-access = free }}</ref><ref name="PUB00001431">{{cite journal | vauthors = Bulet P, Cociancich S, Reuland M, Sauber F, Bischoff R, Hegy G, Van Dorsselaer A, Hetru C, Hoffmann JA | display-authors = 6 | title = A novel insect defensin mediates the inducible antibacterial activity in larvae of the dragonfly Aeschna cyanea (Paleoptera, Odonata) | journal = European Journal of Biochemistry | volume = 209 | issue = 3 | pages = 977–84 | date = November 1992 | pmid = 1425705 | doi = 10.1111/j.1432-1033.1992.tb17371.x | doi-access = free }}</ref> 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.<ref name = "Hanson_2019">{{cite journal | vauthors = Hanson MA, Dostálová A, Ceroni C, Poidevin M, Kondo S, Lemaitre B | title = Synergy and remarkable specificity of antimicrobial peptides in vivo using a systematic knockout approach | journal = eLife | volume = 8 | date = February 2019 | article-number = e44341 | pmid = 30803481 | pmc = 6398976 | doi = 10.7554/eLife.44341 | doi-access = free }}</ref> 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.<ref name = "Hanson_2019"/>
== 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,<ref name="varkey">{{cite journal | vauthors = Varkey J, Singh S, Nagaraj R | title = Antibacterial activity of linear peptides spanning the carboxy-terminal beta-sheet domain of arthropod defensins | journal = Peptides | volume = 27 | issue = 11 | pages = 2614–23 | date = November 2006 | pmid = 16914230 | doi = 10.1016/j.peptides.2006.06.010 | s2cid = 21104756 }}</ref> similar to findings in mammalian defensins.<ref>{{cite journal | vauthors = Varkey J, Nagaraj R | title = Antibacterial activity of human neutrophil defensin HNP-1 analogs without cysteines | journal = Antimicrobial Agents and Chemotherapy | volume = 49 | issue = 11 | pages = 4561–6 | date = November 2005 | pmid = 16251296 | pmc = 1280114 | doi = 10.1128/AAC.49.11.4561-4566.2005 }}</ref> 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.<ref name="varkey" />
A schematic representation of peptides from the arthropod defensin family is shown below.
+----------------------------+ | | {{not a typo|xxCxxxxxxxxxxxxxxCxxxCxxxxxxxxxCxxxxxCxCxx}} | | | | +---|---------------+ | +-----------------+ 'C': conserved cysteine involved in a disulfide bond.
==Relation to other defensins==
Sequence similarities have been reported between the arthropod defensins and mammalian defensins.<ref name="pmid21980497">{{cite journal | vauthors = Rosa RD, Santini A, Fievet J, Bulet P, Destoumieux-Garzón D, Bachère E | title = Big defensins, a diverse family of antimicrobial peptides that follows different patterns of expression in hemocytes of the oyster Crassostrea gigas | journal = PLOS ONE | volume = 6 | issue = 9 | article-number = e25594 | date = 2011 | pmid = 21980497 | pmc = 3182236 | doi = 10.1371/journal.pone.0025594 | bibcode = 2011PLoSO...625594R | doi-access = free }}</ref><ref name="Lambert_1989" /> However it appears that defensins of vertebrates, arthropods, plants, and fungi arose independently.<ref name="Shafee_2016">{{cite journal | vauthors = Shafee TM, Lay FT, Hulett MD, Anderson MA | title = The Defensins Consist of Two Independent, Convergent Protein Superfamilies | journal = Molecular Biology and Evolution | volume = 33 | issue = 9 | pages = 2345–56 | date = September 2016 | pmid = 27297472 | doi = 10.1093/molbev/msw106 | doi-access = free }}</ref> This is supported by 3D structural differences between arthropod defensins and vertebrate beta defensins.<ref name="PUB00001593">{{cite journal | vauthors = Hanzawa H, Shimada I, Kuzuhara T, Komano H, Kohda D, Inagaki F, Natori S, Arata Y | display-authors = 6 | title = 1H nuclear magnetic resonance study of the solution conformation of an antibacterial protein, sapecin | journal = FEBS Letters | volume = 269 | issue = 2 | pages = 413–20 | date = September 1990 | pmid = 2401368 | doi = 10.1016/0014-5793(90)81206-4 | bibcode = 1990FEBSL.269..413H | s2cid = 30637946 | doi-access = free }}</ref> 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.<ref name = "Shafee_2016" />
==Activity against non-microbial cells==
Defensins of mammals display anti-cancer activities in vitro,<ref name="Deslouches_2017">{{cite journal | vauthors = Deslouches B, Di YP | title = Antimicrobial peptides with selective antitumor mechanisms: prospect for anticancer applications | journal = Oncotarget | volume = 8 | issue = 28 | pages = 46635–46651 | date = July 2017 | pmid = 28422728 | pmc = 5542299 | doi = 10.18632/oncotarget.16743 }}</ref> and down-regulation of human beta-defensin 1 is associated with increased risk of prostate cancer and clear-cell carcinomas.<ref name="Donald_2003">{{cite journal | vauthors = Donald CD, Sun CQ, Lim SD, Macoska J, Cohen C, Amin MB, Young AN, Ganz TA, Marshall FF, Petros JA | title = Cancer-specific loss of beta-defensin 1 in renal and prostatic carcinomas | journal = Laboratory Investigation; A Journal of Technical Methods and Pathology | volume = 83 | issue = 4 | pages = 501–5 | date = April 2003 | pmid = 12695553 | doi = 10.1097/01.LAB.0000063929.61760.F6| doi-access = free }}</ref> 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.<ref>{{cite journal | vauthors = Parvy JP, Yu Y, Dostalova A, Kondo S, Kurjan A, Bulet P, Lemaitre B, Vidal M, Cordero JB | title = The antimicrobial peptide defensin cooperates with tumour necrosis factor to drive tumour cell death in Drosophila. | journal = eLife | date = July 2019 | volume = 8 | article-number = e45061 | doi = 10.7554/eLife.45061 | pmid = 31358113 | pmc = 6667213 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Dawson KP, Abbott GD, Allan J | title = Acute respiratory infection in childhood: a study of parental prescribing patterns and advice sources | journal = The New Zealand Medical Journal | volume = 96 | issue = 734 | pages = 481–2 | date = June 1983 | pmid = 6602314 }}</ref>
Overactive immune signalling is also implicated in age-associated neurodegeneration,<ref name="Kounatidis_2017">{{cite journal | vauthors = Kounatidis I, Chtarbanova S, Cao Y, Hayne M, Jayanth D, Ganetzky B, Ligoxygakis P | title = NF-κB Immunity in the Brain Determines Fly Lifespan in Healthy Aging and Age-Related Neurodegeneration | journal = Cell Reports | volume = 19 | issue = 4 | pages = 836–848 | date = April 2017 | pmid = 28445733 | pmc = 5413584 | doi = 10.1016/j.celrep.2017.04.007 }}</ref> and overexpression of defensin leads to increased degradation of brain tissue.<ref name="Cao_2013">{{cite journal | vauthors = Cao Y, Chtarbanova S, Petersen AJ, Ganetzky B | title = Dnr1 mutations cause neurodegeneration in Drosophila by activating the innate immune response in the brain | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 110 | issue = 19 | pages = E1752–60 | date = May 2013 | pmid = 23613578 | pmc = 3651420 | doi = 10.1073/pnas.1306220110| bibcode = 2013PNAS..110E1752C | doi-access = free }}</ref>
==Notes== {{reflist}}
== Further reading == {{refbegin}} * {{cite journal | vauthors = Cornet B, Bonmatin JM, Hetru C, Hoffmann JA, Ptak M, Vovelle F | title = Refined three-dimensional solution structure of insect defensin A | journal = Structure | volume = 3 | issue = 5 | pages = 435–48 | date = May 1995 | pmid = 7663941 | doi = 10.1016/S0969-2126(01)00177-0 | doi-access = free }} {{refend}}
== References == *{{InterPro content|IPR001542}} * {{PROSITE|PDOC00356}} - Arthropod defensins in PROSITE (=source of figure)
{{DEFAULTSORT:Arthropod Defensin}} Category:Defensins Category:Toxins Category:Peripheral membrane proteins Category:Invertebrate immunology Category:Long stubs with short prose
{{membrane-protein-stub}}