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Membrane Proteins

Volume 1063 of the series Methods in Molecular Biology pp 159-180

Date:

On the Role of NMR Spectroscopy for Characterization of Antimicrobial Peptides

  • Fernando PorcelliAffiliated withDepartment of Chemistry, University of MinnesotaDepartment of Biochemistry, Molecular Biology, & Biophysics, University of Minnesota
  • , Ayyalusamy RamamoorthyAffiliated withDepartment of Chemistry, University of Michigan
  • , George BaranyAffiliated withDepartment of Chemistry, University of Minnesota
  • , Gianluigi VegliaAffiliated withDepartment of Chemistry, University of MinnesotaDepartment of Biochemistry, Molecular Biology, & Biophysics, University of Minnesota

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Abstract

Antimicrobial peptides (AMPs) provide a primordial source of immunity, conferring upon eukaryotic cells resistance against bacteria, protozoa, and viruses. Despite a few examples of anionic peptides, AMPs are usually relatively short positively charged polypeptides, consisting of a dozen to about a hundred amino acids, and exhibiting amphipathic character. Despite significant differences in their primary and secondary structures, all AMPs discovered to date share the ability to interact with cellular membranes, thereby affecting bilayer stability, disrupting membrane organization, and/or forming well-defined pores. AMPs selectively target infectious agents without being susceptible to any of the common pathways by which these acquire resistance, thereby making AMPs prime candidates to provide therapeutic alternatives to conventional drugs. However, the mechanisms of AMP actions are still a matter of intense debate. The structure–function paradigm suggests that a better understanding of how AMPs elicit their biological functions could result from atomic resolution studies of peptide–lipid interactions. In contrast, more strict thermodynamic views preclude any roles for three-dimensional structures. Indeed, the design of selective AMPs based solely on structural parameters has been challenging. In this chapter, we will focus on selected AMPs for which studies on the corresponding AMP–lipid interactions have helped reach an understanding of how AMP effects are mediated. We will emphasize the roles of both liquid- and solid-state NMR spectroscopy for elucidating the mechanisms of action of AMPs.

Key words

Antimicrobial peptides Solution NMR Solid-state NMR Lipid membranes