Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
What determines the activity of antimicrobial and cytolytic peptides in model membranes.
Clark KS, Svetlovics J, McKeown AN, Huskins L, Almeida PF.
???displayArticle.abstract???
We previously proposed three hypotheses relating the mechanism of antimicrobial and cytolytic peptides in model membranes to the Gibbs free energies of binding and insertion into the membrane [Almeida, P. F., and Pokorny, A. (2009) Biochemistry 48, 8083-8093]. Two sets of peptides were designed to test those hypotheses, by mutating of the sequences of δ-lysin, cecropin A, and magainin 2. Peptide binding and activity were measured on phosphatidylcholine membranes. In the first set, the peptide charge was changed by mutating basic to acidic residues or vice versa, but the amino acid sequence was not altered much otherwise. The type of dye release changed from graded to all-or-none according to prediction. However, location of charged residues in the sequence with the correct spacing to form salt bridges failed to improve binding. In the second set, the charged and other key residues were kept in the same positions, whereas most of the sequence was significantly but conservatively simplified, maintaining the same hydrophobicity and amphipathicity. This set behaved completely different from predicted. The type of release, which was expected to be maintained, changed dramatically from all-or-none to graded in the mutants of cecropin and magainin. Finally, contrary to the hypotheses, the results indicate that the Gibbs energy of binding to the membrane, not the Gibbs energy of insertion, is the primary determinant of peptide activity.
Almeida,
Binding and permeabilization of model membranes by amphipathic peptides.
2010, Pubmed
Almeida,
Binding and permeabilization of model membranes by amphipathic peptides.
2010,
Pubmed Almeida,
Mechanisms of antimicrobial, cytolytic, and cell-penetrating peptides: from kinetics to thermodynamics.
2009,
Pubmed BARTLETT,
Phosphorus assay in column chromatography.
1959,
Pubmed Ehrenstein,
Electrically gated ionic channels in lipid bilayers.
1977,
Pubmed Fitton,
Physicochemical studies on delta haemolysin, a staphylococcal cytolytic polypeptide.
1981,
Pubmed Fitton,
The amino acid sequence of the delta haemolysin of Staphylococcus aureus.
1980,
Pubmed Frazier,
Investigation of domain formation in sphingomyelin/cholesterol/POPC mixtures by fluorescence resonance energy transfer and Monte Carlo simulations.
2007,
Pubmed Gesell,
Two-dimensional 1H NMR experiments show that the 23-residue magainin antibiotic peptide is an alpha-helix in dodecylphosphocholine micelles, sodium dodecylsulfate micelles, and trifluoroethanol/water solution.
1997,
Pubmed
,
Xenbase Giangaspero,
Amphipathic alpha helical antimicrobial peptides.
2001,
Pubmed Gregory,
A quantitative model for the all-or-none permeabilization of phospholipid vesicles by the antimicrobial peptide cecropin A.
2008,
Pubmed Gregory,
Magainin 2 revisited: a test of the quantitative model for the all-or-none permeabilization of phospholipid vesicles.
2009,
Pubmed
,
Xenbase Guarnera,
How does a simplified-sequence protein fold?
2009,
Pubmed Hällbrink,
Cargo delivery kinetics of cell-penetrating peptides.
2001,
Pubmed Hristova,
An experiment-based algorithm for predicting the partitioning of unfolded peptides into phosphatidylcholine bilayer interfaces.
2005,
Pubmed Hultmark,
Insect immunity. Purification and properties of three inducible bactericidal proteins from hemolymph of immunized pupae of Hyalophora cecropia.
1980,
Pubmed Jayasinghe,
Energetics, stability, and prediction of transmembrane helices.
2001,
Pubmed Kaya,
Energetic components of cooperative protein folding.
2000,
Pubmed Kreger,
Purification and properties of staphylococcal delta hemolysin.
1971,
Pubmed Lacroix,
Elucidating the folding problem of alpha-helices: local motifs, long-range electrostatics, ionic-strength dependence and prediction of NMR parameters.
1998,
Pubmed Ladokhin,
Folding of amphipathic alpha-helices on membranes: energetics of helix formation by melittin.
1999,
Pubmed Ladokhin,
CD spectroscopy of peptides and proteins bound to large unilamellar vesicles.
2010,
Pubmed Ladokhin,
Mechanism of leakage of contents of membrane vesicles determined by fluorescence requenching.
1997,
Pubmed Ladokhin,
Leakage of membrane vesicle contents: determination of mechanism using fluorescence requenching.
1995,
Pubmed Lindgren,
Classes and prediction of cell-penetrating peptides.
2011,
Pubmed Ludtke,
Membrane pores induced by magainin.
1996,
Pubmed
,
Xenbase Luo,
Mechanism of helix induction by trifluoroethanol: a framework for extrapolating the helix-forming properties of peptides from trifluoroethanol/water mixtures back to water.
1997,
Pubmed MacCallum,
Transfer of arginine into lipid bilayers is nonadditive.
2011,
Pubmed Marqusee,
Helix stabilization by Glu-...Lys+ salt bridges in short peptides of de novo design.
1987,
Pubmed Matsuzaki,
Orientational and aggregational states of magainin 2 in phospholipid bilayers.
1994,
Pubmed
,
Xenbase Matsuzaki,
An antimicrobial peptide, magainin 2, induced rapid flip-flop of phospholipids coupled with pore formation and peptide translocation.
1996,
Pubmed
,
Xenbase McKeown,
A thermodynamic approach to the mechanism of cell-penetrating peptides in model membranes.
2011,
Pubmed Muñoz,
Development of the multiple sequence approximation within the AGADIR model of alpha-helix formation: comparison with Zimm-Bragg and Lifson-Roig formalisms.
1997,
Pubmed Muñoz,
Elucidating the folding problem of helical peptides using empirical parameters. II. Helix macrodipole effects and rational modification of the helical content of natural peptides.
1995,
Pubmed Muñoz,
Elucidating the folding problem of helical peptides using empirical parameters.
1994,
Pubmed Muñoz,
Elucidating the folding problem of helical peptides using empirical parameters. III. Temperature and pH dependence.
1995,
Pubmed Nickel,
The mystery of nonclassical protein secretion. A current view on cargo proteins and potential export routes.
2003,
Pubmed Papo,
Can we predict biological activity of antimicrobial peptides from their interactions with model phospholipid membranes?
2003,
Pubmed Pokorny,
Mechanism and kinetics of delta-lysin interaction with phospholipid vesicles.
2002,
Pubmed Pokorny,
Kinetics of dye efflux and lipid flip-flop induced by delta-lysin in phosphatidylcholine vesicles and the mechanism of graded release by amphipathic, alpha-helical peptides.
2004,
Pubmed Pokorny,
The activity of the amphipathic peptide delta-lysin correlates with phospholipid acyl chain structure and bilayer elastic properties.
2008,
Pubmed Pokorny,
Temperature and composition dependence of the interaction of delta-lysin with ternary mixtures of sphingomyelin/cholesterol/POPC.
2006,
Pubmed Pokorny,
Permeabilization of raft-containing lipid vesicles by delta-lysin: a mechanism for cell sensitivity to cytotoxic peptides.
2005,
Pubmed Pouny,
Interaction of antimicrobial dermaseptin and its fluorescently labeled analogues with phospholipid membranes.
1992,
Pubmed Shai,
Mode of action of membrane active antimicrobial peptides.
2002,
Pubmed Shakhnovich,
Protein folding thermodynamics and dynamics: where physics, chemistry, and biology meet.
2006,
Pubmed Silvestro,
The concentration-dependent membrane activity of cecropin A.
1997,
Pubmed Soomets,
Deletion analogues of transportan.
2000,
Pubmed Splith,
Antimicrobial peptides with cell-penetrating peptide properties and vice versa.
2011,
Pubmed Talbot,
Dynamics and orientation of amphipathic peptides in solution and bound to membranes: a steady-state and time-resolved fluorescence study of staphylococcal delta-toxin and its synthetic analogues.
2001,
Pubmed Tamba,
Magainin 2-induced pore formation in the lipid membranes depends on its concentration in the membrane interface.
2009,
Pubmed
,
Xenbase Tamba,
Single giant unilamellar vesicle method reveals effect of antimicrobial peptide magainin 2 on membrane permeability.
2005,
Pubmed
,
Xenbase Thiaudière,
The amphiphilic alpha-helix concept. Consequences on the structure of staphylococcal delta-toxin in solution and bound to lipids.
1991,
Pubmed Tossi,
Amphipathic, alpha-helical antimicrobial peptides.
2000,
Pubmed White,
Membrane protein folding and stability: physical principles.
1999,
Pubmed Wimley,
Interactions between human defensins and lipid bilayers: evidence for formation of multimeric pores.
1994,
Pubmed Wimley,
Experimentally determined hydrophobicity scale for proteins at membrane interfaces.
1996,
Pubmed Wimley,
Direct measurement of salt-bridge solvation energies using a peptide model system: implications for protein stability.
1996,
Pubmed Wimley,
Solvation energies of amino acid side chains and backbone in a family of host-guest pentapeptides.
1996,
Pubmed Yandek,
Mechanism of the cell-penetrating peptide transportan 10 permeation of lipid bilayers.
2007,
Pubmed Yandek,
Wasp mastoparans follow the same mechanism as the cell-penetrating peptide transportan 10.
2009,
Pubmed Yandek,
Small changes in the primary structure of transportan 10 alter the thermodynamics and kinetics of its interaction with phospholipid vesicles.
2008,
Pubmed Yue,
A test of lattice protein folding algorithms.
1995,
Pubmed Zasloff,
Magainins, a class of antimicrobial peptides from Xenopus skin: isolation, characterization of two active forms, and partial cDNA sequence of a precursor.
1987,
Pubmed
,
Xenbase Zasloff,
Antimicrobial peptides of multicellular organisms.
2002,
Pubmed
