Comparison of NMR structures and model-membrane interactions of 15-residue antimicrobial peptides derived from bovine lactoferricin.
LFB (FKCRRWQWRMKKLGA-HN2) is a 15-residue linear antimicrobial peptide derived from bovine lactoferricin, which has antimicrobial activity similar to that of the intact 25-residue disulfide-cyclized peptide. Previous alanine-scan studies, in which all of the residues in LFB were individually replaced with Ala, showed that the 2 tryptophan (Trp) residues of LFB were crucial to its antimicrobial activity. When either Trp6 or Trp8 was replaced with Ala (LFBA6 and LFBA8, respectively), these 2 peptides were almost devoid of antimicrobial activity. We determined the structures of LFB, LFBA6, and LFBA8 bound to membrane-mimetic SDS micelles using NMR spectroscopy, and studied their interactions with different phospholipid-model membranes. The membrane interactions of LFB exhibited little correlation with its antimicrobial activity, suggesting that the mechanism of action of LFB involves intracellular targets. However, the much higher antimicrobial activity of LFB compared with LFBA6 and LFBA8 might result, in part, from the formation of energetically favorable cation-pi interactions observed only in LFB. Information about the importance of Arg and Trp cation-pi interactions will provide insight for the future design of potent antimicrobial peptidomimetics.
Jing
Weiguo
W
Structural Biology Research Group, Department of Biological Sciences, University of Calgary, Calgary, AB T2N 1N4, Canada.
Svendsen
John S
JS
Vogel
Hans J
HJ
D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D002152:Calorimetry, Differential Scanning; D002417:Cattle; D005452:Fluoresceins / Q000378:metabolism; D005453:Fluorescence; D007781:Lactoferrin / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008567:Membranes, Artificial; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D013816:Thermodynamics; D014364:Tryptophan / Q000378:metabolism
D023181:Antimicrobial Cationic Peptides; D005452:Fluoresceins; D008567:Membranes, Artificial; C082171:lactoferricin B; D014364:Tryptophan; D007781:Lactoferrin; C007740:fluorexon