Interaction of melittin with negatively charged phospholipids: Consequences for lipid organization

Batenburg, A. M.; Esch, Jan H. van; Leunissen‐Bijvelt, J.; Verkleij, A.J.; Kruijff, Ben de

doi:10.1016/0014-5793(87)80526-4

Cited by 63 publications

(46 citation statements)

References 26 publications

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“…The stronger affinity of melittin for anionic than for neutral membranes had already been demonstrated [40][41]61 and is corroborated by the present results ( Figure 1). This preference for anionic membranes is likely due to attractive electrostatic interactions associated with the cationic residues of the peptide.…”

Section: Acs Paragon Plus Environmentsupporting

confidence: 92%

“…The titration curves indicated that melittin had a stronger affinity for negatively charged bilayers than for pure DPPC membranes; in the case of DPPC/DPPS 70/30 bilayers, the L/P 50 was shifted to 3.6 and ΔG bind was -30.5 kJ/mol. A consistent increased melittin affinity had already been reported for anionic membranes of PS, of phosphatidylglycerol (PG), or containing unprotonated palmitic acid (PA -) 41,59,61 . This enhanced attraction was proposed to be due to electrostatic interactions.…”

Section: Association To Luvssupporting

confidence: 71%

“…It is well documented that the presence of negatively charged lipids in membranes, such as phosphatidylglycerol (PG), phosphatidylserine (PS), and phosphatidic acid (PA), significantly increases the melittin affinity due to attractive electrostatic interactions [38][39][40][41][42] . However, it was observed that melittin-induced bicellization of membranes was strongly hindered by the presence of anionic lipids in membranes 26,38,40,[43][44] . This observation was proposed to be due to an electrostatic anchoring of the peptide to the interface, preventing the relocation of the peptide deeper in the hydrophobic core, an essential step for the membrane fragmentation.…”

Section: Introductionmentioning

confidence: 99%

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Role of the Cationic C-Terminal Segment of Melittin on Membrane Fragmentation

2016

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The widespread distribution of cationic antimicrobial peptides capable of membrane fragmentation in nature underlines their importance to living organisms. In the present work, we determined the impact of the electrostatic interactions associated with the cationic Cterminal segment of melittin, a 26-amino acid peptide from bee venom (net charge +6), on its binding to model membranes and on the resulting fragmentation. In order to detail the role played by the C-terminal charges, we prepared a melittin analogue for which the 4 cationic amino acids in positions 21 to 24 were substituted with the polar residue citrulline, providing a peptide with the same length and amphiphilicity but with a lower net charge (+2). We compared the peptide bilayer affinity and the membrane fragmentation for bilayers prepared from dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)/1,2-dipalmitoyl-sn-glycero-3-phospho-L-serine (DPPS) mixtures. It is shown that neutralization of the C-terminal considerably increased melittin affinity for zwitterionic membranes. The unfavorable contribution associated with transferring the cationic C-terminal in a less polar environment was reduced, leaving the hydrophobic interactions, which drive the peptide insertion in bilayers, with limited counterbalancing interactions. The presence of negatively charged lipids (DPPS) in bilayers increased melittin binding by introducing attractive electrostatic interactions, the augmentation being, as expected, greater for native melittin than for its citrullinated analogue. The membrane fragmentation power of the peptide was shown to be controlled by electrostatic interactions and could be modulated by the charge carried by both the membrane and the lytic peptide. The analysis of the lipid composition of the extracted fragments from DPPC/DPPS bilayers revealed no lipid specificity. It is proposed that extended phase separations are more susceptible to lead to the extraction of a lipid species in a specific manner than a specific lipid-peptide affinity. The present work on the lipid extraction by melittin and citrullinated melittin with model membranes emphasizes the complex relation between the affinity, the lipid extraction/membrane fragmentation, and the lipid specificity.

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Section: Acs Paragon Plus Environmentsupporting

confidence: 92%

Section: Association To Luvssupporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

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Role of the Cationic C-Terminal Segment of Melittin on Membrane Fragmentation

2016

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“…Both melittin (Dufourcq & Faucon, 1977) and human defensins interact strongly with negatively charged lipid bilayers. Lipid binding of melittin has also been reported to be enhanced (Batenburg et al, 1987) in the presence of the negatively charged lipids. The lipid-to-melittin ratios required to bind melittin completely (c 10 for negatively charged lipids at 100 mM saline, pH 7.3; Batenburg et al, 1987) is comparable to the value calculated by us for binding of human defensin HNP-1 (lipid/defensin = 20 mol/ mol at 100 mM saline, pH 7.4) to the D0PS:DPPC liposomes.…”

Section: Forces Involved In Defensin Destabilization Of Lipid Vesiclesmentioning

confidence: 99%

Defensins promote fusion and lysis of negatively charged membranes

Fujii

Selsted

Eisenberg³

1993

Protein Science

156

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Defensins, a family of cationic peptides isolated from mammalian granulocytes and believed to permeabilize membranes, were tested for their ability to cause fusion and lysis of liposomes. Unlike a-helical peptides whose lytic effects have been extensively studied, the defensins consist primarily of 0-sheet. Defensins fuse and lyse negatively charged liposomes but display reduced activity with neutral liposomes. These and other experiments suggest that fusion and lysis is mediated primarily by electrostatic forces and to a lesser extent, by hydrophobic interactions.Circular dichroism and fluorescence spectroscopy of native defensins indicate that the amphiphilic 0-sheet structure is maintained throughout the fusion process. Taken together, these results support the idea that proteinmediated membrane fusion depends not only on hydrophobic and electrostatic forces but also on the spatial arrangement of the amino acid residues to form a three-dimensional amphiphilic structure, which promotes the efficient mixing of the lipids between membranes. A molecular model for membrane fusion by defensins is presented, which takes into account the contributions of electrostatic forces, hydrophobic interactions, and structural amphiphilicity.

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“…Whereas melittin disrupts PC bilayers into small structures, the peptides exhibit bilayer-stabilizing effects when mixed with phosphatidylethanolamine, a lipid with known tendency for inverse hexagonal phases (H II ) [134]. A different behavior is again observed when melittin is inserted into charged phospholipid membranes such as cardiolipin, 1,2-dioleoyl-sn-glycero-3-phosphatidic acid (DOPA) or egg-phosphatidylglycerol where the peptide induces inverted macroscopic phases (H II or cubic) [135,136]. Electrostatic interactions are not only important during membrane association of cationic amphiphiles, they also have a pronounced effect on the lateral distribution of lipids within the bilayer.…”

Section: Membrane Polymorphismmentioning

confidence: 95%

A dynamic view of peptides and proteins in membranes

Bechinger

2008

Cell. Mol. Life Sci.

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Biological membranes are highly dynamic supramolecular arrangements of lipids and proteins, which fulfill key cellular functions. Relatively few high-resolution membrane protein structures are known to date, although during recent years the structural databases have expanded at an accelerated pace. In some instances the structures of reaction intermediates provide a stroboscopic view on the conformational changes involved in protein function. Other biophysical approaches add dynamic aspects and allow one to investigate the interactions with the lipid bilayers. Membrane-active peptides fulfill many important functions in nature as they act as antimicrobials, channels, transporters or hormones, and their studies have much increased our understanding of polypeptide-membrane interactions. Interestingly several proteins have been identified that interact with the membrane as loose arrays of domains. Such conformations easily escape classical high-resolution structural analysis and the lessons learned from peptides may therefore be instructive for our understanding of the functioning of such membrane proteins.

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Interaction of melittin with negatively charged phospholipids: Consequences for lipid organization

Cited by 63 publications

References 26 publications

Role of the Cationic C-Terminal Segment of Melittin on Membrane Fragmentation

Role of the Cationic C-Terminal Segment of Melittin on Membrane Fragmentation

Defensins promote fusion and lysis of negatively charged membranes

A dynamic view of peptides and proteins in membranes

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