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Antimicrobial Peptides Produced by Selective Pressure Incorporation of Non-canonical Amino Acids
Published on: May 4, 2018
Selective arginines are important for the antibacterial activity and host cell interaction of human alpha-defensin 5
Erik de Leeuw1, Mohsen Rajabi, Guozhang Zou
1University of Maryland Baltimore School of Medicine, Institute of Human Virology, Department of Biochemistry and Molecular Biology, Baltimore, MD 21201, USA. edeleeuw2@ihv.umaryland.edu
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.
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