8GN4

The crystal structure of ZBTB10 ZF1-2 R767Q in complex with telomeric DNA TTAGGG

Summary for 8GN4

• Entry DOI: 10.2210/pdb8gn4/pdb
• Descriptor: Zinc finger and BTB domain-containing protein 10, DNA (5'-D(*TP*TP*AP*GP*GP*GP*TP*TP*AP*TP*A)-3'), DNA (5'-D(*AP*TP*AP*TP*AP*AP*CP*CP*CP*TP*A)-3'), ... (5 entities in total)
• Functional Keywords: telomeric dna binding, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 14797.80

Authors

Li, F.D.,Wang, S.M. (deposition date: 2022-08-22, release date: 2023-08-30, Last modification date: 2024-04-24)

Primary citation

Wang, S.,Xu, Z.,Li, M.,Lv, M.,Shen, S.,Shi, Y.,Li, F.
Structural insights into the recognition of telomeric variant repeat TTGGGG by broad-complex, tramtrack and bric-a-brac - zinc finger protein ZBTB10.
J.Biol.Chem., 299:102918-102918, 2023

PubMed Abstract: Multiple proteins bind to telomeric DNA and are important for the role of telomeres in genome stability. A recent study established a broad-complex, tramtrack and bric-à-brac - zinc finger (BTB-ZF) protein, ZBTB10 (zinc finger and BTB domain-containing protein 10), as a telomeric variant repeat-binding protein at telomeres that use an alternative method for lengthening telomeres). ZBTB10 specifically interacts with the double-stranded telomeric variant repeat sequence TTGGGG by employing its tandem C2H2 zinc fingers (ZF1-2). Here, we solved the crystal structure of human ZBTB10 ZF1-2 in complex with a double-stranded DNA duplex containing the sequence TTGGGG to assess the molecular details of this interaction. Combined with calorimetric analysis, we identified the vital residues in TTGGGG recognition and determined the specific recognition mechanisms that are different from those of TZAP (telomere zinc finger-associated protein), a recently defined telomeric DNA-binding protein. Following these studies, we further identified a single amino-acid mutant (Arg767Gln) of ZBTB10 ZF1-2 that shows a preference for the telomeric DNA repeat TTAGGG sequence. We solved the cocrystal structure, providing a structural basis for telomeric DNA recognition by C2H2 ZF proteins.

PubMed: 36657642
DOI: 10.1016/j.jbc.2023.102918

Experimental method

X-RAY DIFFRACTION (1.9 Å)