8YMZ

Structure of ZBTB43 in complex with CACA containing B-form DNA

Summary for 8YMZ

• Entry DOI: 10.2210/pdb8ymz/pdb
• Descriptor: DNA (5'-D(*TP*CP*AP*CP*AP*CP*AP*TP*AP*CP*AP*CP*AP*CP*T)-3'), DNA (5'-D(*AP*AP*GP*TP*GP*TP*GP*TP*AP*TP*GP*TP*GP*TP*G)-3'), Zinc finger and BTB domain-containing protein 43, ... (4 entities in total)
• Functional Keywords: zbtb43, dna, caca, b-dna, dna binding protein, dna-dna binding protein complex, dna/dna binding protein
• Biological source: Homo sapiens; More
• Total number of polymer chains: 6
• Total formula weight: 38039.50

Authors

Li, X.,Yang, Y. (deposition date: 2024-03-10, release date: 2024-10-09, Last modification date: 2024-11-27)

Primary citation

Yang, Y.,Zhang, S.,Xu, L.,Pan, Y.,Xuan, Y.,Kai, Y.,Chen, X.
Structural insights into the recognition of purine-pyrimidine dinucleotide repeats by zinc finger protein ZBTB43.
Febs J., 291:5002-5014, 2024

PubMed Abstract: 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.

PubMed: 39344089
DOI: 10.1111/febs.17286

Experimental method

X-RAY DIFFRACTION (2.95 Å)