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September 5th, 2025
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molecular biology
bioRxiv

Hydra domain drives SNF2L multimerization and marks ISWI diversification in parasites

Pachano, B.Open in Google Scholar•von Velsen, J.Open in Google Scholar•Corrao, C.Open in Google Scholar•Mas, C.Open in Google Scholar•Pounot, L.Open in Google Scholar•HAKIMI, M.-a.Open in Google Scholar•Bowler, M. W.Open in Google Scholar•Swale, C.Open in Google Scholar

ISWI chromatin remodelers are conserved regulators of nucleosome positioning and chromatin accessibility across eukaryotes, yet their evolutionary diversification is poorly understood. In the apicomplexan parasite Toxoplasma gondii, we identify Hydra, a previously unrecognized globular domain embedded within TgSNF2L, one of two ISWI paralogues. Hydra is structurally unique, lacking homology to any known protein fold, and represents a lineage-specific insertion in an otherwise structurally conserved protein family. Biochemical analyses reveal that the isolated Hydra domain self-assembles into stable oligomers, undergoing reversible equilibrium with its monomeric form. Cryo-electron microscopy analysis reveals discrete globular assemblies, though little consistency could be obtained, suggesting a highly dynamic complex. Deletion of Hydra from full-length TgSNF2L disrupts its intrinsic ability to form higher order oligomers in solution, yielding predominantly monomeric and dimeric species. Functionally, the Hydra-driven multimerization of TgSNF2L modulates its availability for chromatin engagement in response to cell-cycle cues. Hydra thus represents the first reported structural innovation within the ISWI family.

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