Structural malleability of plasticins: Preorganized conformations in solution and relevance for antimicrobial activity

✍ Scribed by F. Bruston; C. Lacombe; K. Zimmermann; C. Piesse; P. Nicolas; C. El Amri

• Book ID: 102761767
• Publisher: Wiley (John Wiley & Sons)
• Year: 2007
• Tongue: English
• Weight: 517 KB
• Volume: 86
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/bip.20703

✦ Synopsis

Abstract

Plasticins (23 long‐residue glycine‐leucine‐rich dermaseptin‐related peptides produced by the skin of South American hylids) have very similar amino acid sequences, hydrophobicities, and amphipathicities, but differ in their membrane‐damaging properties and structurations (i.e. destabilized helix states, β‐hairpin, β‐sheet, and disordered states) at anionic and zwitterionic membrane interfaces. Structural malleability of plasticins in aqueous solutions together with parameters that may govern their ability to fold within β‐hairpin like structures were analyzed through circular dichroism and FTIR spectroscopic studies completed by molecular dynamics simulations in polar mimetic media. The goal of this study was to probe to which extent pre‐existent peptide conformations, i.e. intrinsic “conformational landscape”, may be responsible for variability in bioactive conformation and antimicrobial/hemolytic mechanisms of action of these peptides in relation with their various membrane disturbing properties. All plasticins present a turn region that does not always result in folding into a β‐hairpin shaped conformation. Residue at position 8 plays a major role in initiating the folding, while position 12 is not critical. Conformational stability has no major impact on antimicrobial efficacy. However, preformed β‐hairpin in solution may act as a conformational lock that prevents switch to α‐helical structure. This lock lowers the antimicrobial efficiency and explains subtle differences in potencies of the most active antimicrobial plasticins. © 2007 Wiley Periodicals, Inc. Biopolymers 86: 42–56, 2007.

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