Abstract
As primitive metazoa, sea anemones are rich in various bioactive peptide neurotoxins. These peptides have been applied to neuroscience research tools or directly developed as marine drugs. To date, more than 1100 species of sea anemones have been reported, but only 5% of the species have been used to isolate and identify sea anemone peptide neurotoxins. There is an urgent need for more systematic discovery and study of peptide neurotoxins in sea anemones. In this review, we have gathered the currently available methods from crude venom purification and gene cloning to venom multiomics, employing these techniques for discovering novel sea anemone peptide neurotoxins. In addition, the three-dimensional structures and targets of sea anemone peptide neurotoxins are summarized. Therefore, the purpose of this review is to provide a reference for the discovery, development, and utilization of sea anemone peptide neurotoxins.
Highlights
According to the latest published data in the WoRMS database, 1162 species of sea anemones have been recorded worldwide, and high-throughput transcriptome sequencing shows that there are more than 100 different peptide sequences in each sea anemone to date [5, 45]
Among the sea anemone peptide neurotoxins found by traditional crude venom isolates, the most common cysteine pattern is CXC-C-C-CC, and these toxins mainly act on the neurotoxins that act on voltage-gated sodium (NaV) channel and on acid-sensing ion channel (ASIC), the KV channel, and others [58,59,60,61,62]
Multiomics has constructed a set of research strategies for sea anemone toxins based on integrated correlation analysis of transcriptomics and proteomics, which have been proven to be effective, and high-throughput methods to identify a large number of sea anemone toxin sequences (Fig. 3) [139, 141]
Summary
Traditional isolation and purification of sea anemone toxin are usually performed directly from the crude venom. Among the sea anemone peptide neurotoxins found by traditional crude venom isolates, the most common cysteine pattern is CXC-C-C-CC, and these toxins mainly act on the NaV channel and on ASIC, the KV channel, and others [58,59,60,61,62]. Examples of neurotoxins with the same cysteine pattern (CXC-C-C-CC) include APETx1, APETx2, and Anthopleurin-A These toxins act on the KV channel, ASIC, and NaV channel, respectively [58, 60, 77]. In addition to the main CXC-C-C-CC pattern, there are many other cysteine patterns such as C-C-C-C, C-C-C-C-C-C, C-CC-C-C-C-C, C-C-CC-C-C-C-C, C-C-C-C-C-C-C-C, and C-C-C-C-C-CC-CCC, which are found in sea anemone peptide neurotoxins. The cysteine patterns of sea anemone peptide neurotoxins can act on targets such as the KV channel and TRPA1, and some patterns do not have known targets [30, 73, 74]
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