{"id":"doi:10.3390/toxins18100434","kind":"article","title":"Molecular Characterization of Soritesidine Reveals a Novel Marine Sponge DNase I-like Toxin","authors":["Watari H","Nakano K","Kitano M","Kageyama H","Tanaka Y","Ishibashi Y","Sakai R"],"author_count":7,"year":2026,"published":"2026-10-09","venue":"Toxins","cited_by":0,"doi":"10.3390/toxins18100434","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.3390/toxins18100434","archive_url":"https://space-kitty.com/papers/doi:10.3390/toxins18100434","updated":null,"pmid":"42931525","pmcid":null,"openalex_id":null,"pdf_url":null,"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_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":false,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Molecular Characterization of Soritesidine Reveals a Novel Marine Sponge DNase I-like Toxin\" by Watari H, Nakano K, Kitano M et al., https://doi.org/10.3390/toxins18100434, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"protein-design","name":"AI Protein Design & Structure Prediction","domain_slug":"biotech"}],"cited_in_dossiers":[]}