Structural studies of antimicrobial peptides provide insight into their mechanisms of action

Research output: Chapter in Book/Report/Conference proceedingChapter

4 Scopus citations

Abstract

This chapter reviews structural studies of antimicrobial peptides (AMPs), with a focus on human defensins and cathelicidins. Also discussed are the major steps for structural determination of AMPs by nuclear magnetic resonance spectroscopy, including bacterial expression and purification, sample preparations, data collection, sequential signal assignments, structure calculations, validation and coordinate deposition. A variety of three-dimensional structures (α-helices, β-strands, αβ-fold and non-αβ structures) have been discovered for AMPs, which can induce similar biophysical consequences in membranes such as positive curvature or lipid domain formation. Therefore, it is the amphipathic surface, not polypeptide backbone scaffolds, that is essential for the antimicrobial activity of AMPs. A proper presentation of side chains (e.g. cationic and hydrophobic) on the surface of AMPs determines not only membrane perturbation potential, but also other biological functions. Reduction in hydrophobicity is a fundamental strategy to improve peptide selectivity. Structures of AMPs in complex with membranes or non-membrane targets also form the foundation for engineering a new generation of antimicrobials that will supplement or replace traditional resistant antibiotics.

Original languageEnglish (US)
Title of host publicationAntimicrobial Peptides
Subtitle of host publicationDiscovery, Design and Novel Therapeutic Strategies
PublisherCABI Publishing
Pages141-168
Number of pages28
ISBN (Print)9781845936570
StatePublished - Nov 5 2010

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)
  • Agricultural and Biological Sciences(all)

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  • Cite this

    Wang, G. (2010). Structural studies of antimicrobial peptides provide insight into their mechanisms of action. In Antimicrobial Peptides: Discovery, Design and Novel Therapeutic Strategies (pp. 141-168). CABI Publishing.