An integrative structural study of the human full-length RAD52 at 2.2 Å resolution.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
08 Aug 2024
08 Aug 2024
Historique:
received:
11
02
2024
accepted:
27
07
2024
medline:
8
8
2024
pubmed:
8
8
2024
entrez:
7
8
2024
Statut:
epublish
Résumé
Human RAD52 (RAD52) is a DNA-binding protein involved in many DNA repair mechanisms and genomic stability maintenance. In the last few years, this protein was discovered to be a promising novel pharmacological target for anticancer strategies. Although the interest in RAD52 has exponentially grown in the previous decade, most information about its structure and mechanism still needs to be elucidated. Here, we report the 2.2 Å resolution cryo-EM reconstruction of the full-length RAD52 (FL-RAD52) protein. This allows us to describe the hydration shell of the N-terminal region of FL-RAD52, which is structured in an undecamer ring. Water molecules coordinate with protein residues to promote stabilization inside and among the protomers and within the inner DNA binding cleft to drive protein-DNA recognition. Additionally, through a multidisciplinary approach involving SEC-SAXS and computational methods, we comprehensively describe the highly flexible and dynamic organization of the C-terminal portion of FL-RAD52. This work discloses unprecedented structural details on the FL-RAD52, which will be critical for characterizing its mechanism of action and inhibitor development, particularly in the context of novel approaches to synthetic lethality and anticancer drug discovery.
Identifiants
pubmed: 39112549
doi: 10.1038/s42003-024-06644-1
pii: 10.1038/s42003-024-06644-1
doi:
Substances chimiques
Rad52 DNA Repair and Recombination Protein
0
RAD52 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
956Subventions
Organisme : Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research)
ID : IG 2018 Id.21386
Informations de copyright
© 2024. The Author(s).
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