# Molecular Characterization of Soritesidine Reveals a Novel Marine Sponge DNase I-like Toxin

Article · Watari H, Nakano K, Kitano M, Kageyama H, Tanaka Y, Ishibashi Y, Sakai R

- Archive id: doi:10.3390/toxins18100434
- Published: 2026-10-09
- Venue: Toxins
- DOI: https://doi.org/10.3390/toxins18100434
- PMID: 42931525
- Citations: 0
- Source URL: https://doi.org/10.3390/toxins18100434
- Provenance: europepmc

## Abstract

Soritesidine (SOR) is a potent proteinaceous toxin from the marine sponge Spongosorites sp. that is toxic to mammalian cells, brine shrimp larvae, sea hare embryos, and mice. Although SOR exhibits divalent metal ion-dependent DNase activity, its molecular identity and mechanism of action remained unknown. We determined the amino acid sequence of SOR and investigated its cellular mode of action. Degenerate PCR, 3'-RACE, inverse PCR, and nested PCR identified an open reading frame encoding a 947-amino-acid acidic protein. The deduced sequence showed no substantial similarity to known proteins except for approximately 30% sequence identity to a hypothetical protein from the marine α-proteobacterium Euryhalocaulis caribicus . Analysis of the AlphaFold 3-predicted N-terminal domain using Foldseek and structural superposition revealed a DNase I-like fold with a catalytic architecture similar to that of vertebrate DNase I. A recombinant N-terminal fragment (residues 1-310, N-SOR) exhibited DNA cleavage activity, supporting the assignment of this region as a DNase I-like endonuclease domain. The recombinant fragment lacked detectable cytotoxicity, suggesting that regions outside the N-terminal DNase I-like domain contribute to the cytotoxicity of SOR. Fluorescence imaging showed that SOR entered cells and accumulated in the nucleus, whereas its cellular uptake was attenuated at 4 °C, suggesting the involvement of an energy-dependent internalization pathway. Immunostaining revealed increased γH2AX signals in the nuclei of SOR-treated cells, indicating activation of a DNA damage response. Together, these findings identify SOR as an unusual multidomain protein toxin containing a functional DNase I-like domain and provide a molecular basis for further investigation of its cytotoxic mechanism.

_Abstract reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [AI Protein Design & Structure Prediction](https://space-kitty.com/topics/protein-design)

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