title: Study of the interaction of human defensins with cell membrane models: relationships between structure and biological activity.
abstract: The HNP-1, HNP-2, and HNP-3 defensins are human antimicrobial peptides produced in response to microbial invasion. Their properties are distinct, with a more potent action for HNP-3. In this study, the relationship between their structural dissimilarities and their different microbial actions was evaluated by molecular dynamics simulation. Structural determinants related to their intra- and intermolecular interactions were defined for each HNP using a simplified membrane model consisting of a water/n-hexane interface. The hydrophobic portion of the HNPs promotes their diffusion to the interface with a concomitant, slight change in the structure induced by the intermolecular electrostatic interactions between the HPN molecules and the interface. As a consequence, different orientations are probably adopted by the HNPs at the interface, which may explain their different actions. The interaction of HNP-1 and HNP-2 with the surfaces was also studied using Langmuir monolayers as a biomimetic system. It was found that peptides adsorb rapidly at n-hexane/water interfaces as well as at phospholipid Langmuir monolayers but not at the air/liquid interface. This reveals that the presence of an organic phase is required for the exposure of the hydrophobic groups of the peptides. In addition, adsorption kinetics and surface pressure-area isotherms for Langmuir monolayers suggested that the lipid-peptide interaction is strongly influenced by the monolayer electrical charge and packing, depending also on the HPN structure. This study supports a model in which defensins, acting in a dimeric form, are able to disrupt membranes. The model also shows that the individual structures of the HNPs are responsible for their different actions on microbes.
authors.affiliation: Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, 14040-901 Ribeirão Preto-S. P., Brazil. marcos.lourenzoni@gmail.com
authors.forename: Marcos R
authors.initials: MR
authors.lastname: Lourenzoni
authors.forename: Adriana M
authors.initials: AM
authors.lastname: Namba
authors.forename: Luciano
authors.initials: L
authors.lastname: Caseli
authors.forename: Léo
authors.initials: L
authors.lastname: Degrève
authors.forename: Maria E D
authors.initials: ME
authors.lastname: Zaniquelli
mesh_terms: D000327:Adsorption; D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism*; D003198:Computer Simulation; D023082:Defensins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011312:Pressure; D017434:Protein Structure, Tertiary; D011817:Rabbits; D016415:Sequence Alignment; D055672:Static Electricity; D013329:Structure-Activity Relationship; D013499:Surface Properties; D013696:Temperature