> Details

Karl, Leonhard A; Galanti, Lorenzo; Bantele, Susanne CS; Metzner, Felix; Šafarić, Barbara; Rajappa, Lional; Foster, Benjamin; Pires, Vanessa Borges; Bansal, Priyanka; Chacin, Erika; Basquin, Jerôme; Duderstadt, Karl E; Kurat, Christoph F; Bartke, Till; Hopfner, Karl-Peter; Pfander, Boris

A SAM-key domain required for enzymatic activity of the Fun30 nucleosome remodeler

Reference
management

Bookmarks

Remove from
bookmarks

Share this on Whatsapp

Close

Bookmarks



You can manage bookmarks using lists, please log in to your user account for this.
  • Media type: E-Article
  • Title: A SAM-key domain required for enzymatic activity of the Fun30 nucleosome remodeler
  • Contributor: Karl, Leonhard A; Galanti, Lorenzo; Bantele, Susanne CS; Metzner, Felix; Šafarić, Barbara; Rajappa, Lional; Foster, Benjamin; Pires, Vanessa Borges; Bansal, Priyanka; Chacin, Erika; Basquin, Jerôme; Duderstadt, Karl E; Kurat, Christoph F; Bartke, Till; Hopfner, Karl-Peter; Pfander, Boris
  • Published: Life Science Alliance, LLC, 2023
  • Published in: Life Science Alliance, 6 (2023) 9, Seite e202201790
  • Language: English
  • DOI: 10.26508/lsa.202201790
  • ISSN: 2575-1077
  • Keywords: Health, Toxicology and Mutagenesis ; Plant Science ; Biochemistry, Genetics and Molecular Biology (miscellaneous) ; Ecology
  • Origination:
  • Footnote:
  • Description: Fun30 is the prototype of the Fun30-SMARCAD1-ETL subfamily of nucleosome remodelers involved in DNA repair and gene silencing. These proteins appear to act as single-subunit nucleosome remodelers, but their molecular mechanisms are, at this point, poorly understood. Using multiple sequence alignment and structure prediction, we identify an evolutionarily conserved domain that is modeled to contain a SAM-like fold with one long, protruding helix, which we term SAM-key. Deletion of the SAM-key within budding yeast Fun30 leads to a defect in DNA repair and gene silencing similar to that of thefun30Δ mutant. In vitro, Fun30 protein lacking the SAM-key is able to bind nucleosomes but is deficient in DNA-stimulated ATPase activity and nucleosome sliding and eviction. A structural model based on AlphaFold2 prediction and verified by crosslinking-MS indicates an interaction of the long SAM-key helix with protrusion I, a subdomain located between the two ATPase lobes that is critical for control of enzymatic activity. Mutation of the interaction interface phenocopies the domain deletion with a lack of DNA-stimulated ATPase activation and a nucleosome-remodeling defect, thereby confirming a role of the SAM-key helix in regulating ATPase activity. Our data thereby demonstrate a central role of the SAM-key domain in mediating the activation of Fun30 catalytic activity, thus highlighting the importance of allosteric activation for this class of enzymes.
  • Access State: Open Access