Establishing a reference array for the CS-αβ superfamily of defensive peptides.

D Ellen K Tarr

doi:10.1186/s13104-016-2291-0

Abstract

Background“Invertebrate defensins” belong to the cysteine-stabilized alpha-beta (CS-αβ), also known as the scorpion toxin-like, superfamily. Some other peptides belonging to this superfamily of defensive peptides are indistinguishable from “defensins,” but have been assigned other names, making it unclear what, if any, criteria must be met to qualify as an “invertebrate defensin.” In addition, there are other groups of defensins in invertebrates and vertebrates that are considered to be evolutionarily unrelated to those in the CS-αβ superfamily. This complicates analyses and discussions of this peptide group. This paper investigates the criteria for classifying a peptide as an invertebrate defensin, suggests a reference cysteine array that may be helpful in discussing peptides in this superfamily, and proposes that the superfamily (rather than the name “defensin”) is the appropriate context for studying the evolution of invertebrate defensins with the CS-αβ fold.MethodsCS-αβ superfamily sequences were identified from previous literature and BLAST searches of public databases. Sequences were retrieved from databases, and the relevant motifs were identified and used to create a conceptual alignment to a ten-cysteine reference array. Amino acid sequences were aligned in MEGA6 with manual adjustments to ensure accurate alignment of cysteines. Phylogenetic analyses were performed in MEGA6 (maximum likelihood) and MrBayes (Bayesian).ResultsAcross invertebrate taxa, the term “defensin” is not consistently applied based on number of cysteines, cysteine spacing pattern, spectrum of antimicrobial activity, or phylogenetic relationship. The analyses failed to reveal any criteria that unify “invertebrate defensins” and differentiate them from other defensive peptides in the CS-αβ superfamily. Sequences from various groups within the CS-αβ superfamily of defensive peptides can be described by a ten-cysteine reference array that aligns their defining structural motifs.ConclusionsThe proposed ten-cysteine reference array can be used in addition to current nomenclature to compare sequences in the CS-αβ superfamily and clarify their features relative to one another. This will facilitate analysis and discussion of “invertebrate defensins” in an appropriate evolutionary context, rather than relying on nomenclature.Electronic supplementary materialThe online version of this article (doi:10.1186/s13104-016-2291-0) contains supplementary material, which is available to authorized users.

Highlights

Defensin nomenclature has a complex history (Table 1)
This paper investigates the criteria for classifying a peptide as an invertebrate defensin, suggests a reference cysteine array that may be helpful in discussing peptides in the cysteine-stabilized alpha-beta (CS-αβ) superfamily, and proposes that the superfamily is the appropriate context for studying the evolution of invertebrate defensins with the CS-αβ fold
Insect defensins are described as having the pattern C1–C4, C2–C5, C3–C6; nematode antibacterial factors” (ABFs) have C1–C5, C2–C6, C3–C7, C4–C8

Summary

Introduction

Defensin nomenclature has a complex history (Table 1). “Defensins” originally referred to a set of three human neutrophil peptides that show activity against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Cryptococcus neoformans, and herpes simplex virus, type 1 [1]. The general term “defensin” seemed appropriate due to the broad spectrum of activity. These peptides are 29–30 amino acids long, contain six cysteines that form three disulfide bonds, and are homologous to a group of six peptides from rabbit neutrophils [2, 3]. The term “insect defensin” was proposed by Lambert et al in their description of two small cysteine-rich peptides from Phormia terranovae (phormicins) [4].

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Conclusion