Effect of cholesterol on the polymorphism of dipalmitoylphosphatidylcholine/melittin complexes: an NMR study

Monette, Martine; Calsteren, Marie‐Rose Van; Lafleur, Michel

doi:10.1016/0005-2736(93)90217-n

Cited by 46 publications

(51 citation statements)

References 24 publications

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“…65 For example, a number of studies have shown that cholesterol has a condensing effect on membranes, which decreases the ability of membrane-associating helices to penetrate into the lipid headgroup region. 66–68 In M2-5Ala, the amphipathic helix is further away from the membrane surface and therefore is not as sensitive to changes in bilayer properties. Furthermore, there is some evidence for a specific cholesterol-binding site within the amphipathic helix in the M2 protein.…”

Section: Discussionmentioning

confidence: 99%

A Budding-Defective M2 Mutant Exhibits Reduced Membrane Interaction, Insensitivity to Cholesterol, and Perturbed Interdomain Coupling

et al. 2017

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Influenza A M2 is a membrane-associated protein with a C-terminal amphipathic helix that plays a cholesterol-dependent role in viral budding. An M2 mutant with alanine substitutions in the C-terminal amphipathic helix is deficient in viral scission. With the goal of providing atomic-level understanding of how the wild-type protein functions, we used a multipronged site-directed spin labeling electron paramagnetic resonance spectroscopy (SDSL-EPR) approach to characterize the conformational properties of the alanine mutant. We spin-labeled sites in the transmembrane (TM) domain and the C-terminal amphipathic helix (AH) of wild-type (WT) and mutant M2, and collected information on line shapes, relaxation rates, membrane topology, and distances within the homotetramer in membranes with and without cholesterol. Our results identify marked differences in the conformation and dynamics between the WT and the alanine mutant. Compared to WT, the dominant population of the mutant AH is more dynamic, shallower in the membrane, and has altered quaternary arrangement of the C-terminal domain. While the AH becomes more dynamic, the dominant population of the TM domain of the mutant is immobilized. The presence of cholesterol changes the conformation and dynamics of the WT protein, while the alanine mutant is insensitive to cholesterol. These findings provide new insight into how M2 may facilitate budding. We propose the AH−membrane interaction modulates the arrangement of the TM helices, effectively stabilizing a conformational state that enables M2 to facilitate viral budding. Antagonizing the properties of the AH that enable interdomain coupling within M2 may therefore present a novel strategy for anti-influenza drug design.

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Section: Discussionmentioning

confidence: 99%

A Budding-Defective M2 Mutant Exhibits Reduced Membrane Interaction, Insensitivity to Cholesterol, and Perturbed Interdomain Coupling

et al. 2017

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“…This is similar to the solubilization of membranes by detergents. Interestingly, micellization of melittin specifically occurs in membranes composed of pure saturated phosphatidylcholines and has an interesting dependence on the lipid phase transition temperature (liquid crystalline-to-gel state phase transition of the pure lipid, T m ) (Monette et al 1993). Though the morphology of liquid crystalline bilayer remains unaltered in presence of low concentration of melittin (~5 mol%), the presence of intermediate amounts of melittin induces the liposome to fragment into small particles (micelles) upon lowering of temperature (below T m ) to form gel phase.…”

Section: Micellization and Fusion Of Bilayersmentioning

confidence: 99%

“…These studies conclude that melittin induces a reorganization of lipid assemblies which include vesicularization of multibilayers, fusion of small lipid vesicles, fragmentation into discs and micelles depending on the experimental conditions. Interestingly, the presence of cholesterol in membranes inhibits melittin-induced fusion and formation of small discs (Monette et al 1993;Pott and Dufourc 1995). In contrast, melittin exhibits bilayer-stabilizing effects when mixed with phosphatidylethanolamine membranes under conditions where the pure lipid arranges in a hexagonal phase (H II ) (Batenburg et al 1988).…”

Section: Micellization and Fusion Of Bilayersmentioning

confidence: 99%

Melittin: a Membrane-active Peptide with Diverse Functions

2007

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Melittin is the principal toxic component in the venom of the European honey bee Apis mellifera and is a cationic, hemolytic peptide. It is a small linear peptide composed of 26 amino acid residues in which the amino-terminal region is predominantly hydrophobic whereas the carboxy-terminal region is hydrophilic due to the presence of a stretch of positively charged amino acids. This amphiphilic property of melittin has resulted in melittin being used as a suitable model peptide for monitoring lipid-protein interactions in membranes. In this review, the solution and membrane properties of melittin are highlighted, with an emphasis on melittin-membrane interaction using biophysical approaches. The recent applications of melittin in various cellular processes are discussed.

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“…At high peptide concentrations small objects form (Figure 4d; Dufourcq et al, 1986;Monette et al, 1993). Using stopped-flow fluorescence spectroscopy the penetration of melittin into the hydrophobic region of the bilayer has been identified as the ratelimiting step during incorporation into liquid crystalline bilayer (Sekharam et al, 1991).…”

Section: Detergent-like Propertiesmentioning

confidence: 99%

Structure and Function of Membrane-Lytic Peptides

Bechinger

2004

Critical Reviews in Plant Sciences

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Effect of cholesterol on the polymorphism of dipalmitoylphosphatidylcholine/melittin complexes: an NMR study

Cited by 46 publications

References 24 publications

A Budding-Defective M2 Mutant Exhibits Reduced Membrane Interaction, Insensitivity to Cholesterol, and Perturbed Interdomain Coupling

A Budding-Defective M2 Mutant Exhibits Reduced Membrane Interaction, Insensitivity to Cholesterol, and Perturbed Interdomain Coupling

Melittin: a Membrane-active Peptide with Diverse Functions

Structure and Function of Membrane-Lytic Peptides

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