Effect of Lipid Composition on the “Membrane Response” Induced by a Fusion Peptide

Volynsky, Pavel E.; Polyansky, Anton A.; Simakov, Nikolay A.; Arseniev, and Alexander S.; Efremov, Roman G.

doi:10.1021/bi0514562

Cited by 31 publications

(37 citation statements)

References 28 publications

(43 reference statements)

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“…As shown in Table 2, the presence of the peptide has small effect on the average “global” equilibrium parameters. The difference between the pure lipids and the protein/lipid system observed in our simulation is comparable to those observed using other force fields [64], [65]. For comparison, the same properties and the hydration of lipids for DOPC/DOPS bilayer without IAPP were also present in Table 2.…”

Section: Resultssupporting

confidence: 83%

Conformations of Islet Amyloid Polypeptide Monomers in a Membrane Environment: Implications for Fibril Formation

Duan¹,

Fan²,

Huo

2012

PLoS ONE

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The amyloid fibrils formed by islet amyloid polypeptide (IAPP) are associated with type II diabetes. One of the proposed mechanisms of the toxicity of IAPP is that it causes membrane damage. The fatal mutation of S20G human IAPP was reported to lead to early onset of type II diabetes and high tendency of amyloid formation in vitro. Characterizing the structural features of the S20G mutant in its monomeric state is experimentally difficult because of its unusually fast aggregation rate. Computational work complements experimental studies. We performed a series of molecular dynamics simulations of the monomeric state of human variants in the membrane. Our simulations are validated by extensive comparisons with experimental data. We find that a helical disruption at His18 is common to both human variants. An L-shaped motif of S20G mutant is observed in one of the conformational families. This motif that bends at His18 resembles the overall topology of IAPP fibrils. The conformational preorganization into the fibril-like topology provides a possible explanation for the fast aggregation rate of S20G IAPP.

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Section: Resultssupporting

confidence: 83%

Conformations of Islet Amyloid Polypeptide Monomers in a Membrane Environment: Implications for Fibril Formation

Duan¹,

Fan²,

Huo

2012

PLoS ONE

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“…The order parameter for the associating lipids in the NK2/DPPG system (Figure 12(A)) is slightly decreased at the methylene atoms close to the head group as compared with nonassociating lipids, indicating the peptide‐induced disorder in the lipid acyl chains that are in close proximity to the binding site. This finding agrees with previous simulation on membrane‐bound peptide18, 19, 60, 64. Moreover, it is consistent with experiments that monitor the interaction of a peptide with the condense phase membrane, i.e.…”

Section: Resultssupporting

confidence: 93%

Membrane association and selectivity of the antimicrobial peptide NK‐2: a molecular dynamics simulation study

Pimthon

Willumeit‐Römer²,

Lendlein

et al. 2009

Journal of Peptide Science

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In an effort to better understand the initial mechanism of selectivity and membrane association of the synthetic antimicrobial peptide NK‐2, we have applied molecular dynamics simulation techniques to elucidate the interaction of the peptide with the membrane interfaces. A homogeneous dipalmitoylphosphatidylglycerol (DPPG) and a homogeneous dipalmitoylphosphatidylethanolamine (DPPE) bilayers were taken as model systems for the cytoplasmic bacterial and human erythrocyte membranes, respectively. The results of our simulations on DPPG and DPPE model membranes in the gel phase show that the binding of the peptide, which is considerably stronger for the negatively charged DPPG lipid bilayer than for the zwitterionic DPPE, is mostly governed by electrostatic interactions between negatively charged residues in the membrane and positively charged residues in the peptide. In addition, a characteristic distribution of positively charged residues along the helix facilitates a peptide orientation parallel to the membrane interface. Once the peptides reside close to the membrane surface of DPPG with the more hydrophobic side chains embedded into the membrane interface, the peptide initially disturbs the respective bilayer integrity by a decrease of the order parameter of lipid acyl chain close to the head group region, and by a slightly decrease in bilayer thickness. We found that the peptide retains a high content of helical structure on the zwitterionic membrane‐water interface, while the loss of α‐helicity is observed within a peptide adsorbed onto negatively charged lipid membranes. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.

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“…Bridging increases after surface membrane saturation by the charged peptide. Modelisation studies suggest that the amphipathic fusion peptide E5 of influenza virus binds strongly and at a deeper distance from the aqueous interface in fluid dimirystoylphosphatidylcholine membranes compared to a rigid dipalmytoylphosphatidylcholine membrane [29]. Here, we observe that membrane fluidity also favours bridging.…”

Section: Discussionmentioning

confidence: 49%

The Homeodomain Derived Peptide Penetratin Induces Curvature of Fluid Membrane Domains

et al. 2008

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BackgroundProtein membrane transduction domains that are able to cross the plasma membrane are present in several transcription factors, such as the homeodomain proteins and the viral proteins such as Tat of HIV-1. Their discovery resulted in both new concepts on the cell communication during development, and the conception of cell penetrating peptide vectors for internalisation of active molecules into cells. A promising cell penetrating peptide is Penetratin, which crosses the cell membranes by a receptor and metabolic energy-independent mechanism. Recent works have claimed that Penetratin and similar peptides are internalized by endocytosis, but other endocytosis-independent mechanisms have been proposed. Endosomes or plasma membranes crossing mechanisms are not well understood. Previously, we have shown that basic peptides induce membrane invaginations suggesting a new mechanism for uptake, “physical endocytosis”.Methodology/Principal FindingsHerein, we investigate the role of membrane lipid phases on Penetratin induced membrane deformations (liquid ordered such as in “raft” microdomains versus disordered fluid “non-raft” domains) in membrane models. Experimental data show that zwitterionic lipid headgroups take part in the interaction with Penetratin suggesting that the external leaflet lipids of cells plasma membrane are competent for peptide interaction in the absence of net negative charges. NMR and X-ray diffraction data show that the membrane perturbations (tubulation and vesiculation) are associated with an increase in membrane negative curvature. These effects on curvature were observed in the liquid disordered but not in the liquid ordered (raft-like) membrane domains.Conclusions/SignificanceThe better understanding of the internalisation mechanisms of protein transduction domains will help both the understanding of the mechanisms of cell communication and the development of potential therapeutic molecular vectors. Here we showed that the membrane targets for these molecules are preferentially the fluid membrane domains and that the mechanism involves the induction of membrane negative curvature. Consequences on cellular uptake are discussed.

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Effect of Lipid Composition on the “Membrane Response” Induced by a Fusion Peptide

Cited by 31 publications

References 28 publications

Conformations of Islet Amyloid Polypeptide Monomers in a Membrane Environment: Implications for Fibril Formation

Conformations of Islet Amyloid Polypeptide Monomers in a Membrane Environment: Implications for Fibril Formation

Membrane association and selectivity of the antimicrobial peptide NK‐2: a molecular dynamics simulation study

The Homeodomain Derived Peptide Penetratin Induces Curvature of Fluid Membrane Domains

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