ShK toxin: history, structure and therapeutic applications for autoimmune diseases

Chang, Shih Chieh; Bajaj, Saumya; Chandy, K. George

doi:10.15347/wjs/2018.003

Cited by 6 publications

(4 citation statements)

References 91 publications

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“…The SHK domain was first identified in a potassium channel inhibitor from a sea anemone [91, 92]. A total of 125 SHK domains in 24 genes were identified in L. salmonis which is an extreme number for any arthropod species.…”

Section: Resultsmentioning

confidence: 99%

The salmon louse genome: copepod features and parasitic adaptations

Skern‐Mauritzen

Malde

Eichner

et al. 2021

Preprint

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Arthropods comprise the most populous groups of animals and show an astonishing diversity. Aquatic arthropods belonging to the sub-class Copepoda encompass a range of ecological roles from endo- and ectoparasites to grazers of phytoplankton that link primary producers to higher trophic levels. Despite the important role of copepods in central ecosystem services and their impact as parasites, representative genomic data and genome assemblies are scarce. This limits our opportunities to understand both the specific biology of individual species and unifying copepod genomic features that may govern their capacities to, for example, adapt to a changing environment. Among the copepod parasites we find Lepeophtheirus salmonis, an important ectoparasite that represents a threat to wild salmonid stocks and causes large annual losses to the salmon farming industry. Here we present the salmon louse genome - the first genome of a parasitic copepod that is fully sequenced and annotated. The 695.4 Mbp assembly was validated by a genetic linkage map and comprises 13 autosomes that recombine almost exclusively in males, one autosome that is shielded from recombination in both sexes and a ZZ-ZW style sex chromosome system. The genome assembly contains approximate 60% repetitive regions and comprise 13081 annotated predicted protein-coding genes. The predicted gene set appears to be quite complete as 92.4% of the expected Arthropod genes were found by a BUSCO. The gene annotations were validated by transcriptome sequencing that corresponds to the expected function of selected tissues. Transcriptome sequencing further revealed a marked shift in the gene expression pattern at the transition from the planktonic dispersal phase to the parasitic lifestyle after host attachment. Among other features, genes related to circadian rhythm are downregulated upon attaching to a host - probably reflecting abandoning a planktonic life with diurnal migration. The genome shows several evolutionary signatures including a large expansion of FNII domains, commonly considered vertebrate specific, and an incomplete heme homeostasis pathway suggesting that heme proteins are obtained from the host. The salmon louse has repeatedly demonstrated a large capacity to develop resistance against chemical treatments. Nonetheless, it exhibits low reduced numbers of several genes commonly involved in detoxification; cytochrome P450, ATP-Binding Cassette type transporters and Glutathione S-transferases. Interestingly, only one gene family with a putative detoxification role was expanded: the major vault proteins. Finally, the salmon louse has lost the ability to sustain peroxisomes, a loss apparently shared in the Caligid family but not among copepods in general.

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Section: Resultsmentioning

confidence: 99%

The salmon louse genome: copepod features and parasitic adaptations

Skern‐Mauritzen

Malde

Eichner

et al. 2021

Preprint

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“…They bind to all four subunits in the channel tetramer by two key interactions within the external vestibule – Lys22 occludes the channel pore like a “cork in a bottle,” and Tyr23, together with Lys22, forms a “functional dyad” required for channel block. Many K + channel-blocking peptides exhibit similar blocking mechanism, consisting of a dyad of lysine and neighboring aromatic/aliphatic residue (Chang et al, 2018). With the goal of developing a highly selective K v 1.3 inhibitor, nearly 10 years of effort was made to re-engineer the native ShK.…”

Section: Venom Peptides Targeting Potassium Channelsmentioning

confidence: 99%

Venom-Derived Peptide Modulators of Cation-Selective Channels: Friend, Foe or Frenemy

Bajaj

Han

2019

Front. Pharmacol.

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Ion channels play a key role in our body to regulate homeostasis and conduct electrical signals. With the help of advances in structural biology, as well as the discovery of numerous channel modulators derived from animal toxins, we are moving toward a better understanding of the function and mode of action of ion channels. Their ubiquitous tissue distribution and the physiological relevancies of their opening and closing suggest that cation channels are particularly attractive drug targets, and years of research has revealed a variety of natural toxins that bind to these channels and alter their function. In this review, we provide an introductory overview of the major cation ion channels: potassium channels, sodium channels and calcium channels, describe their venom-derived peptide modulators, and how these peptides provide great research and therapeutic value to both basic and translational medical research.

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“…Due to its effect on effector T cells, this protein became an attractive therapeutic candidate in treating autoimmune diseases [ 2 , 21 ]. One of the ShK-domain-containing proteins from sea anemone was developed as the drug Dalazatide and is currently under phase 1b clinical trials for the treatment of plaque psoriasis, a common autoimmune skin lesion [ 4 , 25 , 26 , 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

ShK-Domain-Containing Protein from a Parasitic Nematode Modulates Drosophila melanogaster Immunity

2022

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A key component to understanding host–parasite interactions is the molecular crosstalk between host and parasite. Excreted/secreted products (ESPs) released by parasitic nematodes play an important role in parasitism. They can directly damage host tissue and modulate host defense. Steinernema carpocapsae, a well-studied parasite of insects releases approximately 500 venom proteins as part of the infection process. Though the identity of these proteins is known, few have been studied in detail. One protein family present in the ESPs released by these nematodes is the ShK family. We studied the most abundant ShK-domain-containing protein in S. carpocapsae ESPs, Sc-ShK-1, to investigate its effects in a fruit fly model. We found that Sc-ShK-1 is toxic under high stress conditions and negatively affects the health of fruit flies. We have shown that Sc-ShK-1 contributes to host immunomodulation in bacterial co-infections resulting in increased mortality and microbial growth. This study provides an insight on ShK-domain-containing proteins from nematodes and suggests these proteins may play an important role in host–parasite interactions.

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ShK toxin: history, structure and therapeutic applications for autoimmune diseases

Abstract: Stichodactyla toxin (ShK) is a 35-residue basic peptide from the sea anemone Stichodactyla helianthus that blocks a number of potassium channels.

Cited by 6 publications

References 91 publications

The salmon louse genome: copepod features and parasitic adaptations

The salmon louse genome: copepod features and parasitic adaptations

Venom-Derived Peptide Modulators of Cation-Selective Channels: Friend, Foe or Frenemy

ShK-Domain-Containing Protein from a Parasitic Nematode Modulates Drosophila melanogaster Immunity

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