Antimicrobial and cell-penetrating peptides induce lipid vesicle fusion by folding and aggregation |
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Authors: | Parvesh Wadhwani Johannes Reichert Jochen Bürck Anne S Ulrich |
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Institution: | (1) Karlsruhe Institute of Technology (KIT), Institute of Biological Interfaces (IBG-2), P.O. Box 3640, 76021 Karlsruhe, Germany;(2) Institute of Organic Chemistry, DFG-Center for Functional Nanostructures, Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany; |
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Abstract: | According to their distinct biological functions, membrane-active peptides are generally classified as antimicrobial (AMP),
cell-penetrating (CPP), or fusion peptides (FP). The former two classes are known to have some structural and physicochemical
similarities, but fusogenic peptides tend to have rather different features and sequences. Nevertheless, we found that many
CPPs and some AMPs exhibit a pronounced fusogenic activity, as measured by a lipid mixing assay with vesicles composed of
typical eukaryotic lipids. Compared to the HIV fusion peptide (FP23) as a representative standard, all designer-made peptides
showed much higher lipid-mixing activities (MSI-103, MAP, transportan, penetratin, Pep1). Native sequences, on the other hand,
were less fusogenic (magainin 2, PGLa, gramicidin S), and pre-aggregated ones were inactive (alamethicin, SAP). The peptide
structures were characterized by circular dichroism before and after interacting with the lipid vesicles. A striking correlation
between the extent of conformational change and the respective fusion activities was found for the series of peptides investigated
here. At the same time, the CD data show that lipid mixing can be triggered by any type of conformation acquired upon binding,
whether α-helical, β-stranded, or other. These observations suggest that lipid vesicle fusion can simply be driven by the
energy released upon membrane binding, peptide folding, and possibly further aggregation. This comparative study of AMPs,
CPPs, and FPs emphasizes the multifunctional aspects of membrane-active peptides, and it suggests that the origin of a peptide
(native sequence or designer-made) may be more relevant to define its functional range than any given name. |
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