scholarly journals Effect of arginine-rich cell penetrating peptides on membrane pore formation and life-times: a molecular simulation study

2014 ◽  
Vol 16 (38) ◽  
pp. 20785-20795 ◽  
Author(s):  
Delin Sun ◽  
Jan Forsman ◽  
Mikael Lund ◽  
Clifford E. Woodward
Keyword(s):  
Molecular Simulation ◽  
Simulation Study ◽  
Pore Formation ◽  
Molecular Simulations ◽  
Cell Penetrating Peptides ◽  
Flip Flop ◽  
Membrane Pore ◽  
Membrane Pores ◽  
Cell Penetrating

Molecular simulations show that arginine-rich peptides can stabilize transient membrane pores induced by lipid flip-flop.

scholarly journals Computational studies of peptide-induced membrane pore formation

2017 ◽  
Vol 372 (1726) ◽  
pp. 20160219 ◽  
Author(s):  
Richard Lipkin ◽  
Themis Lazaridis
Keyword(s):  
Pore Formation ◽  
Coarse Grained ◽  
Future Research ◽  
Implicit Solvent ◽  
Computational Studies ◽  
Membrane Pore ◽  
Membrane Pores ◽  
Solvent Models ◽  
Future Research Directions ◽  
Implicit Solvent Models

A variety of peptides induce pores in biological membranes; the most common ones are naturally produced antimicrobial peptides (AMPs), which are small, usually cationic, and defend diverse organisms against biological threats. Because it is not possible to observe these pores directly on a molecular scale, the structure of AMP-induced pores and the exact sequence of steps leading to their formation remain uncertain. Hence, these questions have been investigated via molecular modelling. In this article, we review computational studies of AMP pore formation using all-atom, coarse-grained, and implicit solvent models; evaluate the results obtained and suggest future research directions to further elucidate the pore formation mechanism of AMPs. This article is part of the themed issue ‘Membrane pores: from structure and assembly, to medicine and technology’.

scholarly journals The single GUV method for revealing the functions of antimicrobial, pore-forming toxin, and cell-penetrating peptides or proteins

2014 ◽  
Vol 16 (30) ◽  
pp. 15752-15767 ◽  
Author(s):  
Md. Zahidul Islam ◽  
Jahangir Md. Alam ◽  
Yukihiro Tamba ◽  
Mohammad Abu Sayem Karal ◽  
Masahito Yamazaki
Keyword(s):  
Rate Constants ◽  
Lipid Membranes ◽  
Pore Formation ◽  
Cell Penetrating Peptides ◽  
Elementary Processes ◽  
Cell Penetrating

The single GUV method provides detailed information on the elementary processes of peptide/protein-induced pore formation in lipid membranes and the entry of peptides into a GUV; specifically, the GUV method provides the rate constants of these processes.

scholarly journals On the solvation of metal ions in liquid ammonia: a molecular simulation study of M(NH2)x(NH3)ycomplexes as a function of pH

RSC Advances ◽  
2017 ◽  
Vol 7 (85) ◽  
pp. 54063-54067 ◽  
Author(s):  
Dirk Zahn
Keyword(s):  
Metal Ions ◽  
Molecular Simulation ◽  
Simulation Study ◽  
Liquid Ammonia ◽  
Molecular Simulations ◽  
Trivalent Metal ◽  
Amide Formation ◽  
Trivalent Metal Ions

The solvation of mono-, di- and trivalent metal ions in liquid ammonia is characterized from molecular simulations using a ‘local’ pKconcept to analyse metal-assisted amide formation.

scholarly journals Bacterial gasdermins reveal an ancient mechanism of cell death

Science ◽  
2022 ◽  
Vol 375 (6577) ◽  
pp. 221-225
Author(s):  
Alex G. Johnson ◽  
Tanita Wein ◽  
Megan L. Mayer ◽  
Brianna Duncan-Lowey ◽  
Erez Yirmiya ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Cell Death ◽  
Pore Formation ◽  
Central Component ◽  
Defense System ◽  
Inhibitory Peptide ◽  
Proteolytic Activation ◽  
Membrane Pore ◽  
Membrane Pores ◽  
Bacteriophage Infection

Ancient origin of cell death Gasdermins are cell death proteins in mammals that form membrane pores in response to pathogen infection. Johnson et al . report that diverse bacteria encode structural and functional homologs of mammalian gasdermins. Like their mammalian counterparts, bacterial gasdermins are activated by caspase-like proteases, oligomerize into large membrane pores, and defend against pathogen—in this case, bacteriophage—infection. Proteolytic activation occurs through the release of a short inhibitory peptide, and many bacterial gasdermins are lipidated to facilitate membrane pore formation. Pyroptotic cell death, a central component of mammalian innate immunity, thus has a shared origin with an ancient antibacteriophage defense system. —SMH

scholarly journals Potassium channels, megapolarization, and water pore formation are key determinants for cationic cell-penetrating peptide translocation into cells

2020 ◽  
Author(s):  
Evgeniya Trofimenko ◽  
Gianvito Grasso ◽  
Mathieu Heulot ◽  
Nadja Chevalier ◽  
Marco A. Deriu ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Pore Formation ◽  
Transmembrane Potential ◽  
Cellular Membrane ◽  
Cell Penetrating Peptides ◽  
Bioactive Molecules ◽  
Cell Penetrating Peptide ◽  
Cell Penetrating

SummaryCell-penetrating peptides (CPPs) allow intracellular delivery of cargo molecules. CPPs provide efficient methodology to transfer bioactive molecules in cells, in particular in conditions when transcription or translation of cargo-encoding sequences is not desirable or achievable. The mechanisms allowing CPPs to enter cells are ill-defined and controversial. This work identifies potassium channels as key regulators of cationic CPP translocation. Using a CRISPR/Cas9-based screening, we discovered that KCNQ5, KCNN4, and KCNK5 positively modulate CPP cellular direct translocation by reducing transmembrane potential (Vm). Cationic CPPs further decrease the Vm to megapolarization values (about −150 mV) leading to the formation of ∼2 nm-wide water pores used by CPPs to access the cell’s cytoplasm. Pharmacological manipulation to lower transmembrane potential boosted CPPs cellular uptake in zebrafish and mouse models. Besides identifying the first genes that regulate CPP translocation, this work characterizes key mechanistic steps used by CPPs to cross cellular membrane. This opens the ground for pharmacological strategies augmenting the susceptibility of cells to capture CPP-linked cargos in vitro and in vivo.

scholarly journals Effect of helical kink in antimicrobial peptides on membrane pore formation

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Alzbeta Tuerkova ◽  
Ivo Kabelka ◽  
Tereza Králová ◽  
Lukáš Sukeník ◽  
Šárka Pokorná ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Pore Formation ◽  
Molecular Level ◽  
Helical Peptides ◽  
Membrane Pore ◽  
Bacterial Membranes ◽  
Membrane Pores ◽  
Helical Peptide ◽  
Toroidal Pore ◽  
The Right

Every cell is protected by a semipermeable membrane. Peptides with the right properties, for example Antimicrobial peptides (AMPs), can disrupt this protective barrier by formation of leaky pores. Unfortunately, matching peptide properties with their ability to selectively form pores in bacterial membranes remains elusive. In particular, the proline/glycine kink in helical peptides was reported to both increase and decrease antimicrobial activity. We used computer simulations and fluorescence experiments to show that a kink in helices affects the formation of membrane pores by stabilizing toroidal pores but disrupting barrel-stave pores. The position of the proline/glycine kink in the sequence further controls the specific structure of toroidal pore. Moreover, we demonstrate that two helical peptides can form a kink-like connection with similar behavior as one long helical peptide with a kink. The provided molecular-level insight can be utilized for design and modification of pore-forming antibacterial peptides or toxins.

scholarly journals Effect of Helical Kink in Antimicrobial Peptides on Membrane Pore Formation

2019 ◽  
Author(s):  
Alzbeta Tuerkova ◽  
Ivo Kabelka ◽  
Tereza Králová ◽  
Lukáš Sukeník ◽  
Šárka Pokorná ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Pore Formation ◽  
Molecular Level ◽  
Helical Peptides ◽  
Membrane Pore ◽  
Bacterial Membranes ◽  
Membrane Pores ◽  
Helical Peptide ◽  
Toroidal Pore ◽  
The Right

AbstractEvery cell is protected by a semipermeable membrane. Peptides with the right properties, e.g. Antimicrobial peptides (AMPs), can disrupt this protective barrier by formation of leaky pores. Unfortunately, matching peptide properties with their ability to selectively form pores in bacterial membranes remains elusive. In particular, the proline/glycine kink in helical peptides was reported to both increase and decrease antimicrobial activity. We used computer simulations and fluorescence experiments to show that a kink in helices affects the formation of membrane pores by stabilizing toroidal pores but disrupting barrel-stave pores. The position of the proline/glycine kink in the sequence further controls the specific structure of toroidal pore. Moreover, we demonstrate that two helical peptides can form a kink-like connection with similar behavior as one long helical peptide with a kink. The provided molecular-level insight can be utilized for design and modification of pore forming antibacterial peptides or toxins.

scholarly journals The role of molecular simulations in understanding the mechanisms of cell-penetrating peptides

2019 ◽  
Vol 24 (9) ◽  
pp. 1821-1835 ◽  
Author(s):  
Lauren M. Reid ◽  
Chandra S. Verma ◽  
Jonathan W. Essex
Keyword(s):  
Molecular Simulations ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating

scholarly journals Membrane perforation by the pore-forming toxin pneumolysin

2019 ◽  
Vol 116 (27) ◽  
pp. 13352-13357 ◽  
Author(s):  
Martin Vögele ◽  
Ramachandra M. Bhaskara ◽  
Estefania Mulvihill ◽  
Katharina van Pee ◽  
Özkan Yildiz ◽  
...  
Keyword(s):  
Lipid Membranes ◽  
Pore Formation ◽  
Line Tension ◽  
Coarse Grained ◽  
Membrane Pore ◽  
Membrane Pores ◽  
Membrane Perforation ◽  
Membrane Spanning ◽  
Dynamics Simulations ◽  
Key Steps

Pneumolysin (PLY), a major virulence factor ofStreptococcus pneumoniae, perforates cholesterol-rich lipid membranes. PLY protomers oligomerize as rings on the membrane and then undergo a structural transition that triggers the formation of membrane pores. Structures of PLY rings in prepore and pore conformations define the beginning and end of this transition, but the detailed mechanism of pore formation remains unclear. With atomistic and coarse-grained molecular dynamics simulations, we resolve key steps during PLY pore formation. Our simulations confirm critical PLY membrane-binding sites identified previously by mutagenesis. The transmembrane β-hairpins of the PLY pore conformation are stable only for oligomers, forming a curtain-like membrane-spanning β-sheet. Its hydrophilic inner face draws water into the protein–lipid interface, forcing lipids to recede. For PLY rings, this zone of lipid clearance expands into a cylindrical membrane pore. The lipid plug caught inside the PLY ring can escape by lipid efflux via the lower leaflet. If this path is too slow or blocked, the pore opens by membrane buckling, driven by the line tension acting on the detached rim of the lipid plug. Interestingly, PLY rings are just wide enough for the plug to buckle spontaneously in mammalian membranes. In a survey of electron cryo-microscopy (cryo-EM) and atomic force microscopy images, we identify key intermediates along both the efflux and buckling pathways to pore formation, as seen in the simulations.

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