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

de Leeuw, Erik; Rajabi, Mohsen; Zou, Guozhang; Pazgier, Marzena; Lu, Wuyuan

doi:10.1016/j.febslet.2009.06.051

« Previous Next »FEBS Letters
Volume 583, Issue 15 , Pages 2507-2512, 6 August 2009

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

Edited by Renee Tsolis

University of Maryland Baltimore School of Medicine, Institute of Human Virology and Department of Biochemistry and Molecular Biology, 725 West Lombard Street, Baltimore, MD 21201, USA

Received 26 June 2009; received in revised form 29 June 2009; accepted 30 June 2009. published online 07 July 2009.

Abstract

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.

Keywords: Human defensin 5, Interleukin 8, Antimicrobial peptide