This non-native structure corresponds to a fragment of the CH1 domain of CBP. Although the CH1 domain in its native form binds 3 zinc ions (Dames et al, PNAS 2002, 99, 5271-5276), this shorter domain binds only one zinc ion, through a different combination of zinc ligating residues. This novel zinc-binding fold is quite remarkable, given that a sequence, taken out of the context of a whole domain, is able to fold into a stable, yet different structure.
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Space filling representations of GNF (blue) and USF1 (red) are shown. These two zinc fingers interact with one another and the residues that are thought to make up the binding interface are shown in yellow. The protein-binding surface of each finger was identified using a combination of chemical shift perturbation studies and mutagenesis.
USF9 has the same zinc ligation topology as USF1 but the two fingers share only 14% sequence identity outside of the zinc ligands (blue). However, USF9 adopts an almost identical fold to USF1, with a short β-hairpin (orange) and an α-helix. Furthermore, USF9 is also able to interact with the N-terminal finger of GATA-1.
U-shaped is a member of the FOG family of transcription factors, which interact with GATA proteins to control gene expression in various tissues. U-shaped has nine zinc fingers. The structure of the first finger of U-shaped (USF1) is very similar to that of a classical zinc finger, consisting of a short β-hairpin (yellow) and an α-helix. The central zinc atom (green) is ligated by 1 His and 3 Cys residues (blue), in contrast to classical fingers, which have a CCHH zinc ligation topology. While many classical fingers bind to DNA, USF1 has been shown to interact with the N-terminal zinc finger of GATA-1.
The structure of GNF consists of two distorted β-hairpins and an α-helix, with a central zinc atom (green) ligated by four cysteine residues (red). GATA-1 interacts with transcription factors from the FOG family using this N-terminal zinc finger. This interaction is crucial for GATA-1’s ability to correctly regulate gene expression in hematopoetic cells.