Structural highlights
Function
[DEF5_HUMAN] Has antimicrobial activity against Gram-negative and Gram-positive bacteria. Defensins are thought to kill microbes by permeabilizing their plasma membrane. All DEFA5 peptides exert antimicrobial activities, but their potency is affected by peptide processing.[1] [2] [3]
Publication Abstract from PubMed
Defensins constitute a major family of natural antimicrobial peptides that protect the host against microbial invasion. Here, we report on the antibacterial properties and cellular interaction of Human Defensin 5 as a function of its positive charge and hydrophobicity. We find that selective replacement of arginine residues in HD-5 by alanine or charge-neutral lysine residues reduces antibacterial killing as well as host cell interaction. We identify arginines at positions 9 and 28 in the HD-5 sequence as particularly important for its function. Replacement of arginine at position 13 to Histidine, as observed in a Crohn's disease patient, reduced bacterial killing strain-selectively. Finally, we find that HD-5 interacts with host cells via receptor-mediated mechanisms.
Selective arginines are important for the antibacterial activity and host cell interaction of human alpha-defensin 5.,de Leeuw E, Rajabi M, Zou G, Pazgier M, Lu W FEBS Lett. 2009 Aug 6;583(15):2507-12. Epub 2009 Jul 7. PMID:19589339[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ghosh D, Porter E, Shen B, Lee SK, Wilk D, Drazba J, Yadav SP, Crabb JW, Ganz T, Bevins CL. Paneth cell trypsin is the processing enzyme for human defensin-5. Nat Immunol. 2002 Jun;3(6):583-90. Epub 2002 May 20. PMID:12021776 doi:10.1038/ni797
- ↑ Ericksen B, Wu Z, Lu W, Lehrer RI. Antibacterial activity and specificity of the six human {alpha}-defensins. Antimicrob Agents Chemother. 2005 Jan;49(1):269-75. PMID:15616305 doi:10.1128/AAC.49.1.269-275.2005
- ↑ Szyk A, Wu Z, Tucker K, Yang D, Lu W, Lubkowski J. Crystal structures of human alpha-defensins HNP4, HD5, and HD6. Protein Sci. 2006 Dec;15(12):2749-60. Epub 2006 Nov 6. PMID:17088326 doi:ps.062336606
- ↑ de Leeuw E, Rajabi M, Zou G, Pazgier M, Lu W. Selective arginines are important for the antibacterial activity and host cell interaction of human alpha-defensin 5. FEBS Lett. 2009 Aug 6;583(15):2507-12. Epub 2009 Jul 7. PMID:19589339 doi:10.1016/j.febslet.2009.06.051