The solution structure of the N-terminal zinc finger of GATA-1 reveals a specific binding face for the transcriptional co-factor FOG

Zinc fingers (ZnFs) are generally regarded as DNA-binding motifs. However, a number of recent reports have implicated particular ZnFs in the mediation of protein-protein interactions. The N-terminal ZnF of GATA-1 (NF) is one such finger, having been shown to interact with a number of other proteins, including the recently discovered transcriptional co-factor FOG. Here we s olve the three-dimensional structure of the NF in solution using multidimen sional H-1/N-15 NMR spectroscopy, and we use H-1/N-15 spin relation measure ments to investigate its backbone dynamics. The structure consists of two d istorted beta-hairpins and a single alpha-helix, and is similar to that of the C-terminal ZnF of chicken GATA-1. Comparisons of the NF structure with those of other C-4-type zinc binding motifs, including hormone receptor and LIM domains, also reveal substantial structural homology. Finally, we use the structure to map the spatial locations of NF residues shown by mutagene sis to be essential for FOG binding, and demonstrate that these residues al l lie on a single face of the NE Notably, this face is well removed from th e putative DNA-binding face of the NE an observation which is suggestive of simultaneous roles for the NF; that is, stabilisation of GATA-1 DNA comple xes and recruitment of FOG to GATA-1-controlled promoter regions.