The actions of melittin on membranes

Dempsey, Christopher E.

doi:10.1016/0304-4157(90)90006-x

Cited by 819 publications

(741 citation statements)

References 89 publications

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“…They also found that the rate of micellization was determined by the rate and extent of PEAAc absorption, which in turn was determined by the lateral compressibility of the membrane (16). In comparison, melittin, the most membrane disruptive peptide known, was less effective on a molar basis (17).…”

Section: Discussionmentioning

confidence: 99%

Hemolytic Activity of pH-Responsive Polymer-Streptavidin Bioconjugates

et al. 1999

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Drug delivery systems that increase the rate and/or quantity of drug release to the cytoplasm are needed to enhance cytosolic delivery and to circumvent nonproductive cell trafficking routes. We have previously demonstrated that poly(2-ethylacrylic acid) (PEAAc) has pH-dependent hemolytic properties, and more recently, we have found that poly(2-propylacrylic acid) (PPAAc) displays even greater pHresponsive hemolytic activity than PEAAc at the acidic pHs of the early endosome. Thus, these polymers could potentially serve as endosomal releasing agents in immunotoxin therapies. In this paper, we have investigated whether the pH-dependent membrane disruptive activity of PPAAc is retained after binding to a protein. We did this by measuring the hemolytic activity of PPAAc-streptavidin model complexes with different protein to polymer stoichiometries. Biotin was conjugated to amine-terminated PPAAc, which was subsequently bound to streptavidin by biotin complexation. The ability of these samples to disrupt red blood cell membranes was investigated for a range of polymer concentrations, a range of pH values, and two polymer-to-streptavidin ratios of 3:1 and 1:1. The results demonstrate that (a) the PPAAc-streptavidin complex retains the ability to lyse the RBC lipid bilayers at low pHs, such as those existing in endosomes, and (b) the hemolytic ability of the PPAAc-streptavidin complex is similar to that of the free PPAAc.

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Section: Discussionmentioning

confidence: 99%

Hemolytic Activity of pH-Responsive Polymer-Streptavidin Bioconjugates

et al. 1999

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“…Several naturally occurring peptides have been used to characterize lipid-protein interactions in model membranes (Sitaram and Nagaraj 1999). A particularly interesting peptide which has been widely used is the hemolytic bee venom peptide, melittin (Dempsey 1990).…”

Section: Introductionmentioning

confidence: 99%

“…It is a small linear peptide composed of 26 amino acids (NH 2 -GIGA-VLKVLTTGLPALISWIKRKRQQ-CONH 2 ) in which the amino-terminal region (residues 1-20) is predominantly hydrophobic whereas the carboxy-terminal region (residues 21-26) is hydrophilic due to the presence of a stretch of positively charged amino acids. This amphiphilic property of melittin makes it water soluble and yet it spontaneously associates with natural and artificial membranes (Dempsey 1990;Sansom 1991;Saberwal and Nagaraj 1994). Such a sequence of amino acids, coupled with its amphiphilic nature, is characteristic of many membrane-bound peptides and putative transmembrane helices of membrane proteins (Dempsey 1990;Shai 1995).…”

Section: Introductionmentioning

confidence: 99%

“…This amphiphilic property of melittin makes it water soluble and yet it spontaneously associates with natural and artificial membranes (Dempsey 1990;Sansom 1991;Saberwal and Nagaraj 1994). Such a sequence of amino acids, coupled with its amphiphilic nature, is characteristic of many membrane-bound peptides and putative transmembrane helices of membrane proteins (Dempsey 1990;Shai 1995). This has resulted in melittin being used as a convenient model for monitoring lipid-protein interactions in membranes.…”

Section: Introductionmentioning

confidence: 99%

“…This has resulted in melittin being used as a convenient model for monitoring lipid-protein interactions in membranes. Apart from its powerful hemolytic activity, melittin causes bilayer micellization and membrane fusion and has also been reported to form voltage-dependent ion channels across planar lipid bilayers (Dempsey 1990;Bechinger, 1997).…”

Section: Introductionmentioning

confidence: 99%

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Effect of micellar charge on the conformation and dynamics of melittin

Raghuraman

Chattopadhyay

2004

Eur Biophys J

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Electrostatic interactions play a crucial role in modulating and stabilizing molecular interactions in membranes and membrane-mimetic systems such as micelles. We have monitored the change in the conformation and dynamics of the cationic hemolytic peptide melittin bound to micelles of various charge types, utilizing fluorescence and circular dichroism (CD) spectroscopy. The sole tryptophan of melittin displays a red-edge excitation shift (REES) of 3-6 nm when bound to anionic, nonionic, and zwitterionic micelles. This suggests that melittin is localized in a restricted environment, probably in the interfacial region of the micelles, and this region offers considerable restriction to the reorientational motion of the solvent dipoles around the excited state tryptophan in melittin. Further, the rotational mobility of melittin is considerably reduced in these micelles and is found to be dependent on the surface charge of micelles. Interestingly, our results show that melittin does not partition into cetyltrimethylammonium bromide (CTAB) micelles owing to electrostatic repulsion between melittin and CTAB micelles, both of which carry a positive charge. In addition, the fluorescence lifetime of melittin is modulated in micelles of different charge types. The lowest mean fluorescence lifetime is observed in the case of melittin bound to anionic sodium dodecyl sulfate (SDS) micelles. CD spectroscopy shows that micelles induce significant helicity to melittin, with maximum helicity being induced in the case of melittin bound to SDS micelles. Fluorescence quenching measurements using the neutral aqueous quencher acrylamide show differential accessibility of melittin in various types of micelles. Taken together, our results show that micellar surface charge can modulate the conformation and dynamics of melittin. These results could be relevant to understanding the role of the surface charge of membranes in the interaction of membrane-active, amphiphilic peptides with membranes.

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Stability of secondary structural elements in a solvent-free environment: the α helix

Kaltashov

Fenselau

1997

Proteins

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The stability of the alpha helix as an element of secondary structure is examined in the absence of solvation, in the gas phase. Mass-analyzed ion kinetic energy (MIKE) spectrometry was applied to measure intercharge repulsion and intercharge distance in multiply protonated melittin, a polypeptide known to possess a stable helical structure in a number of different environments. The experimental results, interpreted in combination with molecular mechanics calculations, suggest that triply charged melittin retains its secondary structure in the gas phase. The stability if the alpha-helical conformation of the polypeptide in the absence of solvent molecules reflects the fact that a network of intrinsic helical hydrogen bonds is energetically more favorable than unfolded conformations.

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The actions of melittin on membranes

Cited by 819 publications

References 89 publications

Hemolytic Activity of pH-Responsive Polymer-Streptavidin Bioconjugates

Hemolytic Activity of pH-Responsive Polymer-Streptavidin Bioconjugates

Effect of micellar charge on the conformation and dynamics of melittin

Stability of secondary structural elements in a solvent-free environment: the α helix

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