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alpha defensin wikipedia jump to content main menu main menu move to sidebar hide navigation main page contents current events random article about wikipedia contact us contribute help learn to edit community portal recent changes upload file special pages search search appearance donate create account log in personal tools donate create account log in contents move to sidebar hide top 1 structure 2 functional characteristics 3 human defensins toggle human defensins subsection 3 1 in human plasma 4 gut expression 5 see also 6 references toggle the table of contents alpha defensin 5 languages català čeština فارسی polski русский edit links article talk english read edit view history tools tools move to sidebar hide actions read edit view history general what links here related changes upload file permanent link page information cite this page get shortened url switch to legacy parser print export download as pdf printable version in other projects wikimedia commons wikidata item appearance move to sidebar hide from wikipedia the free encyclopedia mamilian biological material protein family mammalian defensin structure of defensin hnp 3 1 identifiers symbol defensin_1 pfam pf00323 interpro ipr006081 prosite pdoc00242 scop2 1dfn scope supfam tcdb 1 c 19 opm superfamily 54 opm protein 1tv0 available protein structures pdb ipr006081 pf00323 ecod pdbsum alphafold ipr006081 pf00323 alpha defensins are a family of mammalian defensin peptides of the alpha subfamily they are also known as cryptdins and are produced within the small bowel cryptdin is a portmanteau of crypt and defensin defensins are 2 6 kda cationic antimicrobial peptides active against many gram negative and gram positive bacteria fungi and enveloped viruses 2 containing three pairs of intramolecular disulfide bonds on the basis of their size and pattern of disulfide bonding mammalian defensins are classified into alpha beta and theta categories alpha defensins which have been identified in humans monkeys and several rodent species are particularly abundant in neutrophils certain macrophage populations and paneth cells of the small intestine defensins are produced constitutively and or in response to microbial products or proinflammatory cytokines some defensins are also called corticostatins because they inhibit corticotropin stimulated corticosteroid production the mechanism s by which microorganisms are killed and or inactivated by defensins is not understood completely however it is generally believed that killing is a consequence of disruption of the microbial membrane the polar topology of defensins with spatially separated charged and hydrophobic regions allows them to insert themselves into the phospholipid membranes so that their hydrophobic regions are buried within the lipid membrane interior and their charged mostly cationic regions interact with anionic phospholipid head groups and water subsequently some defensins can aggregate to form channel like pores others might bind to and cover the microbial membrane in a carpet like manner the net outcome is the disruption of membrane integrity and function which ultimately leads to the lysis of microorganisms some defensins are synthesized as propeptides which may be relevant to this process alpha defensins of the mouse bowel were historically called cryptdins when first discovered structure edit hnp 1 hnp 2 and hnp 3 are encoded by two genes defa1 and defa3 localized at chromosome 8 location 8p23 1 defa1 and defa3 encode identical peptides except the conversion of the first amino acid from alanine in hnp 1 to aspartic acid in hnp 3 hnp 2 is an n terminally truncated iso form lacking the first amino acid human neutrophil peptides are found in human atherosclerotic arteries inhibit ldl metabolism and fibrinolysis and promote lp a binding 3 like other alpha defensins cryptdins are small 32 36 amino acid long cationic peptides they possess 6 conserved cysteines that form a tridisulfide array with an arrangement of cysteine pairings that typify alpha defensins cryptdins also display a secondary and tertiary structure that is dominated by a three stranded beta sheet the topology that arises from this structure is an amphipathic globular form in which the termini are paired opposite a pole including a cluster of cationic residues 4 sequences of major human α defensins 5 gene aliases peptide sequence defa1 hnp1 human neutrophil peptide 1 acycripaciagerrygtciyqgrlwafcc hnp2 human neutrophil peptide 2 cycripaciagerrygtciyqgrlwafcc defa3 hnp3 human neutrophil peptide 3 dcycripaciagerrygtciyqgrlwafcc defa4 hnp4 human neutrophil peptide 4 vcscrlvfcrrtelrvgncliggvsftycctrv defa5 hd5 human defensin 5 atcycrhgrcatreslsgvceisgrlyrlccr defa6 hd6 human defensin 6 aftchcrrscysteysygtctvmginhrfccl genes encoding cryptdins are located on the proximal arm of mouse chromosome 8 they are similar to other enteric alpha defensins genes in that they involve a two exon structure the first exon encodes an n terminal canonical signal peptide and proregion that is present in the cryptdin precursor the processed mature peptide is encoded by the second exon which is separated from the first exon by a 500 bp intron 6 biosynthesized as precursors possessing an anionic n terminal proregion cryptdins are packaged into the apically directed secretory granules of paneth cells during this process and perhaps succeeding it the precursors are cleaved by matrix metalloproteinase 7 matrilysin mmp 7 as a result of this proteolysis the c terminal mature form is released from the proregion 7 functional characteristics edit with the ability to kill gram positive and gram negative bacteria fungi spirochetes and some enveloped viruses cryptdins are classified as broad spectrum antimicrobial peptides although it is the least expressed of the six isoforms cryptdin 4 is the most bactericidal procryptdins however are nonbactericidal and thus require degradation of the proregion by mmp 7 for activation in response to bacterial antigens paneth cells release their secretory granules into the lumen of intestinal crypts there cryptdins along with other antimicrobial peptides expressed by paneth cells contribute to enteric mucosal innate immunity by clearing the intestinal crypt of potential invading pathogens 8 human defensins edit initially human alpha defensin peptides were isolated from the neutrophils and are thus called human neutrophil peptides 9 human neutrophil peptides are also known as α defensins human neutrophil derived alpha defensins hnps are capable of enhancing phagocytosis by mouse macrophages hnp1 3 have been reported to increase the production of tumor necrosis factor tnf and il 1 while decreasing the production of il 10 by monocytes increased levels of proinflammatory factors e g il 1 tnf histamine and prostaglandin d2 and suppressed levels of il 10 at the site of microbial infection are likely to amplify local inflammatory responses this might be further reinforced by the capacity of some human and rabbit alpha defensins to inhibit the production of immunosuppressive glucocorticoids by competing for the binding of adrenocorticotropic hormone to its receptor moreover human alpha defensins can enhance or suppress the activation of the classical pathway of complement in vitro by binding to solid phase or fluid phase complement c1q respectively the capacity of defensins to enhance phagocytosis promote neutrophil recruitment enhance the production of proinflammatory cytokines suppress anti inflammatory mediators and regulate complement activation argues that defensins upregulate innate host inflammatory defenses against microbial invasion human neutrophil defensin 1 3 and 4 are elevated in nasal aspirates from children with naturally occurring adenovirus infection 10 in one small study a significant increase in alpha defensin levels was detected in t cell lysates of schizophrenia patients in discordant twin pairs unaffected twins also had an increase although not as high as that of their ill siblings 11 the virtual colony count antibacterial assay was originally developed to measure the activity of all six human alpha defensins on the same microplate 12 in human plasma edit hnps have been extensively studied as plasma marker of a range of diseases such as atherosclerosis rheumatic diseases 13 infections 14 cancer 15 preeclampsia 16 and schizophrenia 17 antibodies directed against fully processed hnp 1 seem to have low affinity for the propeptides prohnps a recent study used antibodies directed against prohnps to show that the predominant forms of alpha defensins in plasma are in fact prohnps 18 prohnps are exclusively synthesized by neutrophil precursors in the bone marrow and appear to be very specific markers of granulopoiesis gut expression edit cryptdins are the protein products of a related family of highly polymorphic genes that are specifically expressed by mouse paneth cells at the base of intestinal crypts 19 they were first characterized as products of cdnas derived from mouse small intestinal rna to date over 25 cryptdin encoding transcripts have been described despite the expression of a relatively large number of cryptdin isoforms only 6 cryptdins have been isolated at the protein level conventional nomenclature labels the isoforms cryptdins 1 through 6 in order of discovery the primary structures of cryptdin isoforms are highly homologous most differences between the isoforms lie in the identity of residues at the n and c termini see also edit defensin α defensin β defensin θ defensin cryptdin references edit hill cp yee j selsted me eisenberg d march 1991 crystal structure of defensin hnp 3 an amphiphilic dimer mechanisms of membrane permeabilization science 251 5000 1481 5 bibcode 1991sci 251 1481h doi 10 1126 science 2006422 pmid 2006422 selsted me white sh wimley wc 1995 structure function and membrane integration of defensins curr opin struct biol 5 4 521 527 doi 10 1016 0959 440x 95 80038 7 pmid 8528769 nassar h lavi e akkawi s bdeir k heyman sn raghunath pn tomaszewski j higazi aa oct 2007 alpha defensin link between inflammation and atherosclerosis atherosclerosis 194 2 452 7 doi 10 1016 j atherosclerosis 2006 08 046 pmid 16989837 satchell dp sheynis t shirafuji y kolusheva s ouellette aj jelinek r 2003 interactions of mouse paneth cell alpha defensins and alpha defensin precursors with membranes prosegment inhibition of peptide association with biomimetic membranes j biol chem 278 16 13838 46 doi 10 1074 jbc m212115200 pmid 12574157 bowdish dm davidson dj hancock re 2006 immunomodulatory properties of defensins and cathelicidins antimicrobial peptides and human disease current topics in microbiology and immunology vol 306 pp 27 66 doi 10 1007 3 540 29916 5_2 isbn 978 3 540 29915 8 pmc 7121507 pmid 16909917 cite book journal ignored help ouellette aj darmoul d tran d huttner km yuan j selsted me 1999 peptide localization and gene structure of cryptdin 4 a differentially expressed mouse paneth cell alpha defensin infect immun 67 12 6643 51 doi 10 1128 iai 67 12 6643 6651 1999 pmc 97078 pmid 10569786 wilson c ouellette a satchell d ayabe t lópez boado y stratman j hultgren s matrisian l parks w 1999 regulation of intestinal alpha defensin activation by the metalloproteinase matrilysin in innate host defense science 286 5437 113 7 doi 10 1126 science 286 5437 113 pmid 10506557 ayabe t satchell dp wilson cl parks wc selsted me ouellette aj 2000 secretion of microbicidal alpha defensins by intestinal paneth cells in response to bacteria nat immunol 1 2 113 8 doi 10 1038 77783 pmid 11248802 s2cid 23204633 ganz t selsted me szklarek d harwig ss daher k bainton df lehrer ri oct 1985 defensins natural peptide antibiotics of human neutrophils j clin invest 76 4 1427 35 doi 10 1172 jci112120 pmc 424093 pmid 2997278 v s priyadharshini f ramírez jiménez m molina macip et al human neutrophil defensin 1 3 and 4 are elevated in nasal aspirates from children with naturally occurring adenovirus infection canadian respiratory journal vol 2018 article id 1038593 6 pages 2018 https doi org 10 1155 2018 1038593 craddock rm huang jt jackson e et al march 2008 increased alpha defensins as a blood marker for schizophrenia susceptibility mol cell proteomics 7 7 1204 13 doi 10 1074 mcp m700459 mcp200 pmid 18349140 ericksen b wu z lu w lehrer ri 2005 antibacterial activity and specificity of the six human α defensins antimicrob agents chemother 49 1 269 75 doi 10 1128 aac 49 1 269 275 2005 pmc 538877 pmid 15616305 vordenbäumen s sander o bleck e schneider m fischer betz r may jun 2012 cardiovascular disease and serum defensin levels in systemic lupus erythematosus clinical and experimental rheumatology 30 3 364 70 pmid 22510487 panyutich av panyutich ea krapivin va baturevich ea ganz t august 1993 plasma defensin concentrations are elevated in patients with septicemia or bacterial meningitis the journal of laboratory and clinical medicine 122 2 202 7 pmid 8340706 droin n hendra jb ducoroy p solary e aug 20 2009 human defensins as cancer biomarkers and antitumour molecules journal of proteomics 72 6 918 27 doi 10 1016 j jprot 2009 01 002 pmid 19186224 prieto ja panyutich av heine rp january 1997 neutrophil activation in preeclampsia are defensins and lactoferrin elevated in preeclamptic patients the journal of reproductive medicine 42 1 29 32 pmid 9018642 craddock rm huang jt jackson e harris n torrey ef herberth m bahn s july 2008 increased alpha defensins as a blood marker for schizophrenia susceptibility molecular cellular proteomics 7 7 1204 13 doi 10 1074 mcp m700459 mcp200 pmid 18349140 glenthøj a glenthøj aj borregaard n august 2013 prohnps are the principal α defensins of human plasma european journal of clinical investigation 43 8 836 43 doi 10 1111 eci 12114 pmid 23718714 s2cid 205092943 ouellette aj 1997 paneth cells and innate immunity in the crypt microenvironment gastroenterology 113 5 1779 84 doi 10 1053 gast 1997 v113 pm9352884 pmid 9352884 retrieved from https en wikipedia org w index php title alpha_defensin oldid 1339204782 categories defensins peripheral membrane proteins hidden categories articles with short description short description is different from wikidata short description matches wikidata cs1 errors periodical ignored this page was last edited on 19 february 2026 at 13 21 utc page was rendered with parsoid text is available under the creative commons attribution sharealike 4 0 license additional terms may apply by using this site you agree to the terms of use and privacy policy wikipedia is a registered trademark of the wikimedia foundation inc a non profit organization privacy policy about wikipedia disclaimers contact wikipedia legal safety contacts code of conduct developers statistics cookie statement mobile view search search toggle the table of contents alpha defensin 5 languages add topic