Selective arginines are important for the antibacterial activity and host cell interaction of human a-defensin 5

• Published in: FEBS letters Vol. 583; no. 15; pp. 2507 - 2512
• Main Authors: de Leeuw, E, Rajabi, M, Zou, G, Pazgier, M, Lu, W
• Format: Journal Article
• Language: English
• Published: 06.08.2009
• ISSN: 0014-5793
• DOI: 10.1016/j.febslet.2009.06.051

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.