ИСТИНА

Capitellacin is a β-hairpin antimicrobial peptide (AMP) from the marine polychaete Capitella teleta. Capitellacin exhibits antimicrobial activity against a wide range of bacteria, including antibiotic-resistant strains. To establish the mechanism of capitellacin action, we investigated the structure of the peptide in the membrane-mimicking environment, specifically in dodecylphosphocholine (DPC) micelles, using high-resolution NMR spectroscopy. We determined the structures of two forms of capitellacin – a monomeric β-hairpin and a dimer, formed by antiparallel association of the N-terminal β-strands of the peptide. Transitions between these forms occurred with the changes of temperature and the peptide to detergent molar ratio. The dimerization of capitellacin in the membrane-like environment occurs due to the interaction of polar or weakly hydrophobic regions and depends more on the intermolecular interactions (hydrogen bonds, electrostatic and van der Waals interactions) than on the hydrophobic effect. Dimerization is characterized by a negative change in enthalpy and entropy. The topology of both forms of capitellacin in the micelles and the distribution of polar and hydrophobic regions on the molecular surfaces suggested that capitellacin disrupts the membrane integrity according to the “carpet” mechanism. This explains the lower antibacterial, hemolytic and membrane permeabilization activities of capitellacin in comparison with other β-hairpin peptides, which can form pores in the target membranes. A comparative analysis of physicochemical properties of β-hairpin AMPs revealed a positive correlation between the hydrophobicity of the peptide, the stability of its dimers and the hemolytic activity. The results obtained enable us to describe more precisely the mechanism of oligomerization of β-structural peptides in the membrane