Structural insights into the recognition of purine-pyrimidine dinucleotide repeats by zinc finger protein ZBTB43.
crystal structure
protein‐DNA interaction
purine‐pyrimidine repeats
transcription factor
Journal
The FEBS journal
ISSN: 1742-4658
Titre abrégé: FEBS J
Pays: England
ID NLM: 101229646
Informations de publication
Date de publication:
29 Sep 2024
29 Sep 2024
Historique:
revised:
01
09
2024
received:
05
07
2024
accepted:
20
09
2024
medline:
30
9
2024
pubmed:
30
9
2024
entrez:
30
9
2024
Statut:
aheadofprint
Résumé
Purine-pyrimidine repeats (PPRs) can form left-handed Z-form DNA and induce DNA double-strand breaks (DSBs), posing a risk for genomic rearrangements and cancer. The zinc finger (ZF) and BTB domain-containing protein 43 (ZBTB43) is a transcription factor containing two Cys2-His2 (C2H2) and one C3H1 zinc fingers and plays a crucial role in maintaining genomic and epigenomic integrity by converting mutagenic Z-form PPRs to the B-form in prospermatogonia. Despite its importance, the molecular mechanism underlying the recognition of PPRs by ZBTB43 remains elusive. In this study, we determined the X-ray crystal structure of the ZBTB43 ZF1-3 in complex with the B-form DNA containing the CA repeats sequence. The structure reveals that ZF1 and ZF2 primarily recognize the CACA sequence through specific hydrogen-bonding and van der Waals contacts via a quadruple center involving Arg389, Met411, His413, and His414. These interactions were further validated by fluorescence-based DNA-binding assays using mutated ZBTB43 variants. Our structural investigation provides valuable insights into the recognition mechanism of PPRs by ZBTB43 and suggests a potential role for ZBTB43 in the transformation of Z-DNA to B-DNA, contributing to the maintenance of genomic stability.
Banques de données
RefSeq
['NP_001129248.1']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Natural Science Research Project of Anhui Educational Committee
ID : 2022AH030010
Organisme : National Natural Science Foundation of China
ID : 3220979
Organisme : National Natural Science Foundation of China
ID : 32371270
Organisme : Natural Science Foundation of Anhui Province
ID : 2208085QC76
Informations de copyright
© 2024 Federation of European Biochemical Societies.
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