Hydra domain drives SNF2L multimerization and marks ISWI diversification in parasites

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Abstract
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 Tg SNF2L, 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 Tg SNF2L disrupts its intrinsic ability to form higher order oligomers in solution, yielding predominantly monomeric and dimeric species. Functionally, the Hydra-driven multimerization of Tg SNF2L modulates its availability for chromatin engagement in response to cell-cycle cues. Hydra thus represents the first reported structural innovation within the ISWI family.
Funding Information
  • MSD Avenir (DS-2022-0017)
  • Agence Nationale de la Recherche (ANR-11-LABX-0024)
  • Agence Nationale de la Recherche (ANR-21-CE35-0010-01)
  • Agence Nationale de la Recherche (ANR-21-CE15-0002-01)
  • Agence Nationale de la Recherche (ANR-24-CHBS-0008)
  • Agence Nationale de la Recherche (ANR-10-INBS-0005-02)
  • Agence Nationale de la Recherche (ANR-17-EURE-0003)
  • Fondation pour la Recherche Médicale (EQU202103012571)

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