Abstract
Binding of the nuclear factor-Y complex (NF-Y) to the inverted CCAAT-box interferes with
transcription activation through nucleosome reorganization. The three homologous proteins forming the zincfingers
and homeoboxes (ZHX) family interact with the activation domain of NF-Ya to repress transcription.
EachZHX-protein contains two genericC2H2 zinc-fingers (ZNF1 and ZNF2) followed by five homeodomains.
Although the proteins have been related to the occurrence of certain cancers, the function and structure of the
individual ZHX domains are still unknown. Here, we determined the structure of the tandem zinc-finger region
of human ZHX1. Folding and secondary structure predictions combined with expression screening revealed
that the C-terminal extension (E) to ZNF2 could form a single domain with the two hZHX1 zinc-fingers. We
therefore decided to determine the solution structure of the zinc-fingers followed by this extension.Weshowthat
both zinc-fingers adopt canonical ββR-folds in which a zinc ion is coordinated by two cysteine and two histidine
residues. The C-terminal extension to ZNF2 forms two β-strands to make a β-sheet with the β-strands of this
zinc-finger. The ZNF1 and ZNF2-E domains do not show evident contacts and their mutual orientation seems
variable. The high degree of sequence conservation among ZHX family members permitted us to prepare
homology models for ZHX2 and ZHX3, revealing distinct surface characteristics for each family member.
Implications of these structural features for ZHX-functioning in transcription regulation are discussed.
Original language | Undefined/Unknown |
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Pages (from-to) | 4431-4439 |
Number of pages | 9 |
Journal | Biochemistry |
Volume | 48 |
Issue number | 21 |
Publication status | Published - 2009 |