Interactions of histatin 5 and histatin 5-derived peptides with liposome membranes: surface effects, translocation and permeabilization.
A number of cationic antimicrobial peptides, among which are histatin 5 and the derived peptides dhvar4 and dhvar5, enter their target cells and interact with internal organelles. There still are questions about the mechanisms by which antimicrobial peptides translocate across the membrane. We used a liposome model to study membrane binding, translocation and membrane-perturbing capacities of histatin 5, dhvar4 and dhvar5. Despite the differences in amphipathic characters of these peptides, they bound equally well to liposomes, whereas their membrane activities differed remarkably: dhvar4 translocated at the fastest rate, followed by dhvar5, whereas the histatin 5 translocation rate was much lower. The same pattern was seen for the extent of calcein release: highest with dhvar4, less with dhvar5 and almost none with histatin 5. The translocation and disruptive actions of dhvar5 did not seem to be coupled, because translocation occurred on a much longer timescale than calcein release, which ended within a few minutes. We conclude that peptide translocation can occur through peptide-phospholipid interactions, and that this is a possible mechanism by which antimicrobial peptides enter cells. However, the translocation rate was much lower in this model membrane system than that seen in yeast cells. Thus it is likely that, at least for some peptides, additional features promoting the translocation across biological membranes are involved as well.
Den Hertog
Alice L
AL
Department of Dental Basic Sciences, Section Oral Biochemistry, Academic Centre for Dentistry Amsterdam (ACTA), Vrije Universiteit, Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands. al.denhertog@vumc.nl
Wong Fong Sang
Harro W
HW
Kraayenhof
Ruud
R
Bolscher
Jan G M
JG
Van't Hof
Wim
W
Veerman
Enno C I
EC
Nieuw Amerongen
Arie V
AV
D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D005452:Fluoresceins / Q000378:metabolism; D054808:Histatins; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D021381:Protein Transport; D012471:Salivary Proteins and Peptides / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D014357:Trypsin / Q000378:metabolism
D005452:Fluoresceins; C068075:HTN3 protein, human; D054808:Histatins; D008081:Liposomes; D010446:Peptide Fragments; D012471:Salivary Proteins and Peptides; D014357:Trypsin; C007740:fluorexon