Cysteine-stabilized αβ defensins: From a common fold to antibacterial activity

Abstract

Antimicrobial peptides (AMPs) seem to be promising alternatives to common antibiotics, which are facing increasing bacterial resistance. Among them are the cysteine-stabilized αβ defensins. These peptides are small, with a length ranging from 34 to 54 amino acid residues, cysteine-rich and extremely stable, normally composed of an α-helix and three β-strands stabilized by three or four disulfide bonds and commonly found in several organisms. Moreover, animal and plant CSαβ defensins present different specificities, the first being mainly active against bacteria and the second against fungi. The role of the CSαβ-motif remains unknown, but a common antibacterial mechanism of action, based on the inhibition of the cell-wall formation, has already been observed in some fungal and invertebrate defensins. In this context, the present work aims to group the data about CSαβ defensins, highlighting their evolution, conservation, structural characteristics, antibacterial activity and biotechnological perspectives.

Cysteines and Disulfide Bonds as Structure-Forming Units: Insights From Different Domains of Life and the Potential for Characterization by NMR

“…Depending on the spacing of the cysteines and their pairing, three subfamilies (α, β, θ) are defined. Molecules of these classes share a similar structural fold (Lehrer and Lu, 2012;Dias Rde and Franco, 2015) and are facing interest as promising alternatives to conventional antibiotics. Recently, the NMR solution structure of rattusin expanded the structural repertoire of defensins by a scaffold formed by intermolecular disulfide exchanges between dimer units (Min et al, 2017).…”

Structure-Activity Relationships of Insect Defensins

“…The tight arrangement of secondary structural elements is reflected in high stability against heat or proteases. Accordingly, this structural topology is known as cysteine-stabilized αβ motif (CSαβ) and is common among defensin peptides across different organisms, from plants to invertebrates to vertebrates (Dias Rde and Franco, 2015; Tarr, 2016; Shafee et al, 2017). Although all insect defensins share this common structural motif their primary sequence (Figure 1A) as well as their spectrum of antimicrobial activity varies considerably (Table 1).…”

Antimicrobial peptides of invertebrates. Part 1. structure, biosynthesis, and evolution

“…8) are the AMP family most wide spread in nature. Representatives of this family occur both in vertebrate and invertebrate animals, plants, and fungi [111][112][113]. The defensin like peptides are found in myxobacteria [114].…”

“…Therefore, they are also called as CSαβ peptides (cysteine stabilized α helix and β sheet) [113]. This structure is an evolutionary conser vative pattern of a spatial folding of a polypeptide chain.…”