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Dynamics and orientation of a cationic antimicrobial peptide in two membrane-mimetic systems.

ABSTRACT: In order to investigate the functional and structural properties of cationic alpha-helical peptides in two different membranes, we studied the 20-residue peptide maximin H6 in two membrane-mimetic systems by NMR spectroscopy using partially (15)N-labeled peptide and paramagnetic relaxation enhancements. Maximin H6, which is found in skin secretions of frogs of the Bombinae family, attacks gram-negative bacteria and acts haemolytically. While the peptide spontaneously folds into similar structures in both neutral dodecylphosphocholine (DPC) and negatively charged sodium dodecyl sulphate (SDS) micelles, its structure is more flexible in SDS as shown by (15)N relaxation measurements. In addition, it is bound closer to the surface of the micelle and rotated by approximately 70 degrees around its helix axis in the negatively charged membrane surrogate compared to the structure in DPC. This might form the basis for peptide-peptide interactions through a GxxxG motif, which could finally lead to membrane disruption and, thus, preferential attack of negatively charged microbial cell walls.

SUBMITTER: Kosol S

PROVIDER: S-EPMC7128155 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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Dynamics and orientation of a cationic antimicrobial peptide in two membrane-mimetic systems.

Kosol Simone S Zangger Klaus K

Journal of structural biology 20100104 1

In order to investigate the functional and structural properties of cationic alpha-helical peptides in two different membranes, we studied the 20-residue peptide maximin H6 in two membrane-mimetic systems by NMR spectroscopy using partially (15)N-labeled peptide and paramagnetic relaxation enhancements. Maximin H6, which is found in skin secretions of frogs of the Bombinae family, attacks gram-negative bacteria and acts haemolytically. While the peptide spontaneously folds into similar structure ...[more]

PMID: 20045466

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Project description:Most phages of Gram-negative hosts encode spanins for disruption of the outer membrane, the last step in host lysis. However, bioinformatic analysis indicates that ∼15% of these phages lack a spanin gene, suggesting they have an alternate way of disrupting the OM. Here, we show that the T7-like coliphage phiKT causes the explosive cell lysis associated with spanin activity despite not encoding spanins. A putative lysis cassette cloned from the phiKT late gene region includes the hypothetical novel gene 28 located between the holin and endolysin genes and supports inducible lysis in E. coli K-12. Moreover, induction of an isogenic construct lacking gene 28 resulted in divalent cation-stabilized spherical cells rather than lysis, implicating gp28 in OM disruption. Additionally, gp28 was shown to complement the lysis defect of a spanin-null λ lysogen. Gene 28 encodes a 56-amino acid cationic protein with predicted amphipathic helical structure and is membrane-associated after lysis. Urea and KCl washes did not release gp28 from the particulate, suggesting a strong hydrophobic membrane interaction. Fluorescence microscopy supports membrane localization of the gp28 protein prior to lysis. Gp28 is similar in size, charge, predicted fold, and membrane association to the human cathelicidin antimicrobial peptide LL-37. Synthesized gp28 behaved similar to LL-37 in standard assays mixing peptide and cells to measure bactericidal and inhibitory effects. Taken together, these results indicate that phiKT gp28 is a phage-encoded cationic antimicrobial peptide that disrupts bacterial outer membranes during host lysis and thus establishes a new class of phage lysis proteins, the disruptins. Significance We provide evidence that phiKT produces an antimicrobial peptide for outer membrane disruption during lysis. This protein, designated as a disruptin, is a new paradigm for phage lysis and has no similarities to other known lysis genes. Although many mechanisms have been proposed for the function of antimicrobial peptides, there is no consensus on the molecular basis of membrane disruption. Additionally, there is no established genetic system to support such studies. Therefore, the phiKT disruptin may represent the first genetically tractable antimicrobial peptide, facilitating mechanistic analyses.

Dataset Information

Dynamics and orientation of a cationic antimicrobial peptide in two membrane-mimetic systems.

Publications

Dynamics and orientation of a cationic antimicrobial peptide in two membrane-mimetic systems.

Similar Datasets

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