Interactions of mast cell degranulating peptides with model membranes: A comparative biophysical study

Abstract

In the last decade, there has been renewed interest in biologically active peptides in fields like allergy, autoimmune diseases and antibiotic therapy. Mast cell degranulating peptides mimic G-protein receptors, showing different activity levels even among homologous peptides. Another important feature is their ability to interact directly with membrane phospholipids, in a fast and concentration-dependent way. The mechanism of action of peptide HR1 on model membranes was investigated comparatively to other mast cell degranulating peptides (Mastoparan, Eumenitin and Anoplin) to evidence the features that modulate their selectivity. Using vesicle leakage, single-channel recordings and zeta-potential measurements, we demonstrated that HR1 preferentially binds to anionic bilayers, accumulates, folds, and at very low concentrations, is able to insert and create membrane spanning ion-selective pores. We discuss the ion selectivity character of the pores based on the neutralization or screening of the peptides charges by the bilayer head group charges or dipoles.

Chemical and biological characterization of four new linear cationic α-helical peptides from the venoms of two solitary eumenine wasps

“…Similarly the four peptides in our study presented circular dichroism spectra that are characteristic of helical structures with practically equivalent a-helix content, except for EMP-ER, which showed a higher helical content. The experiments of electrical measurements in planar lipid bilayers of anionic asolectin showed that all the new peptides present a pore-or channel-like activity, in both the positive and negative voltage pulses, as previously demonstrated for eumenitin ), anoplin (dos Santos Cabrera et al, 2008 and other mastoparan peptides (Mellor and Sansom, 1990;dos Santos Cabrera et al, 2009). Channels with lower and higher conductance levels were recorded, but the latter ones were less frequent, and formed only in the presence of the non-amidated Cterminal peptides (eumenitin-R and eumenitin-F).…”

Folding propensity of anoplin: A molecular dynamics study of the native peptide and four mutated isoforms

“…A large number of studies have been devoted, in the last years, to the analysis of the Anoplin secondary structure. Although a quantitative picture is still missing, all the results from these studies support the hypothesis that in water Anoplin is essentially unfolded and that adopts an α‐helical structure in membrane‐mimicking environments . The same studies have also shown a correlation between Anoplin antimicrobial activity and some specific structural–chemical determinants, e.g.…”

Polydim-I antimicrobial activity against MDR bacteria and its model membrane interaction

“…Zeta-potential values reflect the remaining charge density which were neither neutralized nor screened. Changes in zeta potential are used to quantify the extension of the interaction between peptides and phospholipid vesicles and changes in size are related to peptides inducing vesicles aggregation or acting in the detergent mode [39]. In the absence of peptide, AZO vesicles are characterized by an average zeta-potential value of -19.7 ± 0.6 mV (ζ 0 ).…”

“…The formation of conductive pores was previously described for other peptides isolated from solitary and social wasp venoms, such as anoplin [61], HR-1 [39], eumenine mastoparan-EF and–ER [34], and eumenitin, eumenitin-F and eumenitin-R [34,62]. Some of these wasp peptides formed rectified pores, whose conductance (or resistance) changes according to the V hold (see [34] Rangel et al, 2011).…”