Simulations reveal that antimicrobial BP100 induces local membrane thinning, slows lipid dynamics and favors water penetration

Franco, Leandro Rezende; Park, Peter; Chaimovich, Hernán; Coutinho, Kaline; Cuccovia, Iolanda M.; Lima, Filipe da Silva

doi:10.1039/d1ra06267k

Cited by 7 publications

(12 citation statements)

References 97 publications

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“…1 B–D) were selected from the Antimicrobial Peptide Database 48 (APD3, https://aps.unmc.edu ) based on their similarity with a previously studied SCHAMP, BP100 (Fig. 1 A) 37 , 38 . They are short peptides (11–13 aminoacids), amphiphilic in alpha-helix conformation, which is their predominant secondary structure when in contact with negatively charged membranes 21 , 36 , 40 , 41 , 43 , 44 .…”

Section: Methodsmentioning

confidence: 99%

“…Previous data suggest negatively charged membranes favor the occurrence of peptide flip 37 , in which the amphiphilic peptide approaches the membrane with its polar side and then it turns, facing the membrane with its non-polar side and burying the peptide into the membrane core. In order to compare with previous results obtained with BP100 37 , 38 , we simulated peptides on a mixed bilayer of palmitoyloleoylphosphatidylcholine (POPC) and palmitoyloleoylphosphatidylglycerol (POPG) in a 1:1 mol/mol ratio. Membranes containing 64 lipids on each leaflet were assembled using PACKMOL 56 and were solvated with the TIP3P water model, with an average of 55 water molecules per lipid.…”

Section: Methodsmentioning

confidence: 99%

“…We coined the term “peptide flip” to describe such dynamical process wherein peptides transition from a solvated state into a membrane-bound state. In addition, single BP100 causes local membrane thinning and negative curvature and slows lipid lateral diffusion 38 . The peptide binds better to the liquid-disordered phase than the liquid-ordered phase in In coarse-grained MD simulations of BP100 on a phase-separated membrane.…”

Section: Introductionmentioning

confidence: 99%

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Vesicle protrusion induced by antimicrobial peptides suggests common carpet mechanism for short antimicrobial peptides

Park,

Matsubara,

Barzotto

et al. 2024

Sci Rep

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Short-cationic alpha-helical antimicrobial peptides (SCHAMPs) are promising candidates to combat the growing global threat of antimicrobial resistance. They are short-sequenced, selective against bacteria, and have rapid action by destroying membranes. A full understanding of their mechanism of action will provide key information to design more potent and selective SCHAMPs. Molecular Dynamics (MD) simulations are invaluable tools that provide detailed insights into the peptide-membrane interaction at the atomic- and meso-scale level. We use atomistic and coarse-grained MD to look into the exact steps that four promising SCHAMPs—BP100, Decoralin, Neurokinin-1, and Temporin L—take when they interact with membranes. Following experimental set-ups, we explored the effects of SCHAMPs on anionic membranes and vesicles at multiple peptide concentrations. Our results showed all four peptides shared similar binding steps, initially binding to the membrane through electrostatic interactions and then flipping on their axes, dehydrating, and inserting their hydrophobic moieties into the membrane core. At higher concentrations, fully alpha-helical peptides induced membrane budding and protrusions. Our results suggest the carpet mode of action is fit for the description of SCHAMPs lysis activity and discuss the importance of large hydrophobic residues in SCHAMPs design and activity.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Vesicle protrusion induced by antimicrobial peptides suggests common carpet mechanism for short antimicrobial peptides

Park,

Matsubara,

Barzotto

et al. 2024

Sci Rep

Self Cite

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“…Besides lipid bilayer thinning and thickening, also the curvature of the membrane is an important aspect regarding its morphology. In biological processes like endocytosis and vesiculation, a change of the membrane's curvature has been observed and plays a crucial role in them 149 . Researchers synthesized the amphipathic helical peptide EpN18 (XSTSSLRRQXKNIVHNYS–amide, X = norleucine) that derived from the N‐terminus of the protein epsin‐1.…”

Section: Membrane Composition/morphology Changes Induced By Peptide I...mentioning

confidence: 99%

“…142 them. 149 Researchers synthesized the amphipathic helical peptide EpN18 (XSTSSLRRQXKNIVHNYS-amide, X = norleucine) that derived from the N-terminus of the protein epsin-1. They found that the incorporation of EpN18 in HeLa cells led to packing defects in the membrane (Figure 12).…”

Section: Membrane Composition/ Morphology Changes Induced By Peptide ...mentioning

confidence: 99%

Artificial peptides to induce membrane denaturation and disruption and modulate membrane composition and fusion

Lāce

Cotroneo

Hesselbarth

et al. 2022

Journal of Peptide Science

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Membranes consisting of phospholipid bilayers are an essential constituent of eukaryotic cells and their compartments. The alteration of their composition, structure, and morphology plays an important role in modulating physiological processes, such as transport of molecules, cell migration, or signaling, but it can also lead to lethal effects. The three main classes of membrane‐active peptides that are responsible for inducing such alterations are cell‐penetrating peptides (CPPs), antimicrobial peptides (AMPs), and fusion peptides (FPs). These peptides are able to interact with lipid bilayers in highly specific and tightly regulated manners. They can either penetrate the membrane, inducing nondestructive, transient alterations, or disrupt, permeabilize, or translocate through it, or induce membrane fusion by generating attractive forces between two bilayers. Because of these properties, membrane‐active peptides have attracted the attention of the pharmaceutical industry, and naturally occurring bioactive structures have been used as a platform for synthetic modification and the development of artificial analogs with optimized therapeutic properties to transport biologically active cargos or serve as novel antimicrobial agents. In this review, we focus on synthetic membrane interacting peptides with bioactivity comparable with their natural counterparts and describe their mechanism of action.

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Venomous Peptides: Molecular Origin of the Toxicity of Snake Venom PLA₂-like Peptides

Coimbra,

Gissler,

Nitor

et al. 2024

JACS Au

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Snakebite envenoming claims 81−138 thousand lives annually, with vipers responsible for many of those. Phospholipase A 2 (PLA 2 ) enzymes and PLA 2 -like proteins are among the most important viper venom toxins. The latter are particularly intriguing, as three decades after their discovery, their molecular mechanism of toxicity is still poorly understood at best. PLA 2 -like proteins destabilize eukaryotic cell membranes through an unknown mechanism, causing an uncontrolled influx of Ca 2+ ions and ultimately triggering cell death. It is now clear that the C-terminal segment is fundamental to the toxicity, as 13-mer peptides with the same sequence exhibit most or all of the activities of the complete PLA 2 -like proteins. To finally clarify the mechanism of toxicity of these venom peptides, we have simulated their interaction with model cell membranes. Molecular dynamics simulations showed that peptides initially dispersed across the cell membrane quickly and spontaneously migrated, aggregated, induced membrane thinning, and formed clear and transient membrane pores. We calculated the potentials of the mean force for Ca 2+ transfer across the cell membranes through the transient pores. The pores significantly lower the free energy barrier for Ca 2+ translocation, an effect that grows with the size of the peptide aggregates and, thus, with the pore radius. Ca 2+ flowed across the membrane through the largest pores with almost no barrier. The permeability of Ca 2+ through the largest pores exceeded the permeability of pharmaceutical drugs by 4 orders of magnitude, revealing the easiness by which Ca 2+ overflows the intracellular medium. These results elucidate the illusive molecular origin of the toxicity of this famous class of snake venom-derived peptides.

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Simulations reveal that antimicrobial BP100 induces local membrane thinning, slows lipid dynamics and favors water penetration

Abstract: MD simulations reveal that BP100 peptide induces local membrane thinning and negative curvature, slows lipid dynamics and increases the water life time in the lipid hydrophobic core and transmembrane water transport in the direction of the peptide.

Cited by 7 publications

References 97 publications

Vesicle protrusion induced by antimicrobial peptides suggests common carpet mechanism for short antimicrobial peptides

Vesicle protrusion induced by antimicrobial peptides suggests common carpet mechanism for short antimicrobial peptides

Artificial peptides to induce membrane denaturation and disruption and modulate membrane composition and fusion

Venomous Peptides: Molecular Origin of the Toxicity of Snake Venom PLA₂-like Peptides

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Simulations reveal that antimicrobial BP100 induces local membrane thinning, slows lipid dynamics and favors water penetration

Abstract: MD simulations reveal that BP100 peptide induces local membrane thinning and negative curvature, slows lipid dynamics and increases the water life time in the lipid hydrophobic core and transmembrane water transport in the direction of the peptide.

Cited by 7 publications

References 97 publications

Vesicle protrusion induced by antimicrobial peptides suggests common carpet mechanism for short antimicrobial peptides

Vesicle protrusion induced by antimicrobial peptides suggests common carpet mechanism for short antimicrobial peptides

Artificial peptides to induce membrane denaturation and disruption and modulate membrane composition and fusion

Venomous Peptides: Molecular Origin of the Toxicity of Snake Venom PLA2-like Peptides

Contact Info

Product

Resources

About

Venomous Peptides: Molecular Origin of the Toxicity of Snake Venom PLA₂-like Peptides