F
IPR016327

Alpha-defensin

InterPro entry
Short nameAlpha-defensin

Description

Mammalian alpha-defensins are expressed primarily in leukocytes and epithelia. They play an important role in the innate and adaptive immune response to microbial infection. There are six cysteine residues and one glycine residue, for an atypical SS-bulge, which are totally conserved in the otherwise diverse sequences of all known mammalian alpha-defensins. There is also a conserved pair of oppositely charged residues (Arg/Glu) that form a salt bridge across a protruding loop in the molecule. The primary function of the salt bridge in HD5 is to ensure correct processing of proHD5 and subsequent stabilisation of mature alpha-defensin in vivo
[2]
.

Human neutrophil alpha-defensins (HNPs) are synthesized in vivo as inactive precursor proteins, i.e. preproHNPs. A series of sequential proteolytic events excise the N-terminal inhibitory pro peptide, leading to defensin maturation and storage in azurophilic granules
[1]
. Human alpha-defensin-1 (HNP1) is a small antimicrobial peptide, which is cytotoxic to tumour cells in vitro and shows inhibitory activity for pathologic neovascularisation in vivo. Intracellularly expressed HNP1 induces tumour cell apoptosis, consequently inhibiting its growth. It might be involved in the host immune response to tumours and as such is a promising basis for HNP1-based gene therapy for cancer
[3]
.

References

1.Impact of pro segments on the folding and function of human neutrophil alpha-defensins. Wu Z, Li X, Ericksen B, de Leeuw E, Zou G, Zeng P, Xie C, Li C, Lubkowski J, Lu WY, Lu W. J. Mol. Biol. 368, 537-49, (2007). View articlePMID: 17355880

2.The conserved salt bridge in human alpha-defensin 5 is required for its precursor processing and proteolytic stability. Rajabi M, de Leeuw E, Pazgier M, Li J, Lubkowski J, Lu W. J. Biol. Chem. 283, 21509-18, (2008). View articlePMID: 18499668

3.Human alpha-defensin-1 inhibits growth of human lung adenocarcinoma xenograft in nude mice. Xu N, Wang YS, Pan WB, Xiao B, Wen YJ, Chen XC, Chen LJ, Deng HX, You J, Kan B, Fu AF, Li D, Zhao X, Wei YQ. Mol. Cancer Ther. 7, 1588-97, (2008). View articlePMID: 18566229

GO terms

molecular function

  • None
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