Summary information and primary citation
- PDB-id
-
5v3j;
DSSR-derived features in text and
JSON formats
- Class
- transferase-DNA
- Method
- X-ray (2.064 Å)
- Summary
- Mousezfp568-znf1-10 in complex with DNA
- Reference
-
Patel A, Yang P, Tinkham M, Pradhan M, Sun MA, Wang Y,
Hoang D, Wolf G, Horton JR, Zhang X, Macfarlan T, Cheng X
(2018): "DNA
Conformation Induces Adaptable Binding by Tandem Zinc
Finger Proteins." Cell,
173, 221-233.e12. doi: 10.1016/j.cell.2018.02.058.
- Abstract
- Tandem zinc finger (ZF) proteins are the largest and
most rapidly diverging family of DNA-binding transcription
regulators in mammals. ZFP568 represses a transcript of
placental-specific insulin like growth factor 2 (Igf2-P0)
in mice. ZFP568 binds a 24-base pair sequence-specific
element upstream of Igf2-P0 via the eleven-ZF array. Both
DNA and protein conformations deviate from the conventional
one finger-three bases recognition, with individual ZFs
contacting 2, 3, or 4 bases and recognizing thymine on the
opposite strand. These interactions arise from a shortened
minor groove caused by an AT-rich stretch, suggesting
adaptability of ZF arrays to sequence variations. Despite
conservation in mammals, mutations at Igf2 and ZFP568
reduce their binding affinity in chimpanzee and humans. Our
studies provide important insights into the evolutionary
and structural dynamics of ZF-DNA interactions that play a
key role in mammalian development and evolution.
