Startseite
English
Erweiterte Suche
Durchblättern nach ...
Publikationen im Überblick
Ansprechpartner
Hilfe
DOI
PMC
 |
|
|
Open Access Gold möglich sobald Verlagsversion bei der ZB eingereicht worden ist.
A SAM-key domain required for enzymatic activity of the Fun30 nucleosome remodeler.
Life Sci. All. 6:19 (2023)
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 the fun30Δ 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.
Altmetric
Weitere Metriken?
Zusatzinfos bearbeiten
[➜Einloggen]
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Chromatin; Atpase; Yeast; Resection; Binding; Family; Rsc; Phosphorylation; Identification; Mechanisms
ISSN (print) / ISBN
2575-1077
e-ISSN
2575-1077
Zeitschrift
Life Science Alliance
Quellenangaben
Band: 6,
Heft: 9,
Artikelnummer: 19
Verlag
EMBO Press
Verlagsort
Heidelberg
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Functional Epigenetics (IFE)
Förderungen
European Research Council
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)
Max Planck Society
European Research Council
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)
Max Planck Society