The Defensins Consist of Two Independent, Convergent Protein Superfamilies

Shafee, Thomas; Lay, Fung T.; Hulett, Mark D.; Anderson, Marilyn A.

doi:10.1093/molbev/msw106

Cited by 122 publications

(162 citation statements)

References 64 publications

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“…Comparisons purely based on primary sequences are error-prone (Grishin, 2001) and conservation within secondary and tertiary structure is higher as compared to the primary sequences (Shafee et al, 2016). Currently only nine peptides have been characterized using solution NMR spectroscopy, including four antifungal, i.e., heliomicin (Lamberty et al, 2001a), drosomycin (Landon et al, 1997), termicin (Da Silva et al, 2003), and ARD1 (Landon et al, 2004) as well as five anti-gram-positive peptides, i.e., phormicin (Cornet et al, 1995), sapecin (Hanzawa et al, 1990), Def-AAA (Landon et al, 2008), lucifensin (Nygaard et al, 2012), and coprisin (Lee et al, 2013).…”

Section: Structure-activity Relationships Of Insect Defensinsmentioning

confidence: 99%

Structure-Activity Relationships of Insect Defensins

Koehbach

2017

Front. Chem.

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Insects make up the largest and most diverse group of organisms on earth with several million species to exist in total. Considering the sheer number of insect species and the vast variety of ways they interact with their environment through chemistry, it is clear that they have significant potential as a source of new lead molecules. They have adapted to a range of ecological habitats and exhibit a symbiotic lifestyle with various microbes such as bacteria and fungi. Accordingly, numerous antimicrobial compounds have been identified including for example defensin peptides. Insect defensins were found to have broad-spectrum activity against various gram-positive/negative bacteria as well as fungi. They exhibit a unique structural topology involving the complex arrangement of three disulfide bonds as well as an alpha helix and beta sheets, which is known as cysteine-stabilized αβ motif. Their stability and amenability to peptide engineering make them promising candidates for the development of novel antibiotics lead molecules. This review highlights the current knowledge regarding the structure-activity relationships of insect defensin peptides and provides basis for future studies focusing on the rational design of novel cysteine-rich antimicrobial peptides.

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Section: Structure-activity Relationships Of Insect Defensinsmentioning

confidence: 99%

Structure-Activity Relationships of Insect Defensins

Koehbach

2017

Front. Chem.

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“…These peptides, along with sapecins identified a year earlier, showed activity primarily against Gram-positive bacteria and appeared to have some sequence homology to the mammalian defensins [4, 5]. It is now clear that observed similarities between insect and mammalian defensins are most likely due to convergence, but the name “defensin” has been retained [6, 7]. Two antifungal peptides with similarity to defensins were isolated from radish [8], and the term “plant defensin” was proposed after cloning of the full-length sequences for these peptides, which have eight cysteines instead of six [9].…”

Section: Introductionmentioning

confidence: 99%

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

Tarr

2016

BMC Res Notes

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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.

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“…In a recent study, Shafee et al [2] proposed the concept of cis- and trans -defensins and suggested they represent two independent and convergent protein superfamilies due to the difference in the pattern of disulfide connectivities. However, the results of our present study clearly demonstrate that this pattern and even the fold type are changeable in evolution of defensins.…”

Section: Discussionmentioning

confidence: 99%

“…These molecules exhibit enormous sequence and structural diversity with at least two distinct protein superfamilies, named cis -and trans -defensins, based on the orientation of the most conserved pair of disulfide bridges [2]. The cis -defensins refer to a group of structurally conserved peptides isolated from plants, fungi and invertebrates whereas the trans -defensins contain structurally diversified members, including big defensins from invertebrates and α-, β- and θ-defensins from vertebrates [2,3]. As one of the most diverse organisms on earth, fungi are emerging as a new source for exploring bioactive compounds, such as defensins [4].…”

Section: Introductionmentioning

confidence: 99%

New fungal defensin-like peptides provide evidence for fold change of proteins in evolution

Gao

Zhu

2017

Bioscience Reports

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Defensins containing a consensus cystine framework, Cys[1]…Cys[2]X3Cys[3]…Cys[4]… Cys[5]X1Cys[6] (X, any amino acid except Cys; …, variable residue numbers), are extensively distributed in a variety of multicellular organisms (plants, fungi and invertebrates) and essentially involved in immunity as microbicidal agents. This framework is a prerequisite for forming the cysteine-stabilized α-helix and β-sheet (CSαβ) fold, in which the two invariant motifs, Cys[2]X3Cys[3]/Cys[5]X1Cys[6], are key determinants of fold formation. By using a computational genomics approach, we identified a large superfamily of fungal defensin-like peptides (fDLPs) in the phytopathogenic fungal genus – Zymoseptoria, which includes 132 structurally typical and 63 atypical members. These atypical fDLPs exhibit an altered cystine framework and accompanying fold change associated with their secondary structure elements and disulfide bridge patterns, as identified by protein structure modelling. Despite this, they definitely are homologous with the typical fDLPs in view of their precise gene structure conservation and identical precursor organization. Sequence and structural analyses combined with functional data suggest that most of Zymoseptoria fDLPs might have lost their antimicrobial activity. The present study provides a clear example of fold change in the evolution of proteins and is valuable in establishing remote homology among peptide superfamily members with different folds.

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The Defensins Consist of Two Independent, Convergent Protein Superfamilies

Cited by 122 publications

References 64 publications

Structure-Activity Relationships of Insect Defensins

Structure-Activity Relationships of Insect Defensins

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

New fungal defensin-like peptides provide evidence for fold change of proteins in evolution

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