Selective arginines are important for the antibacterial activity and host cell interaction of human alpha-defensin 5.
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.
de Leeuw
Erik
E
University of Maryland Baltimore School of Medicine, Institute of Human Virology, Department of Biochemistry and Molecular Biology, Baltimore, MD 21201, USA. edeleeuw2@ihv.umaryland.edu
Rajabi
Mohsen
M
Zou
Guozhang
G
Pazgier
Marzena
M
Lu
Wuyuan
W
D000409:Alanine / Q000378:metabolism; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D001120:Arginine / Q000378:metabolism*; D003424:Crohn Disease / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D023084:alpha-Defensins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; C500225:DEFA5 protein, human; D023084:alpha-Defensins; D001120:Arginine; D000409:Alanine