Model of N-terminal zinc finger of GATA2. Model of ZF1 (yellow ribbon with brown DNA and gray zinc ion), based on the crystal structure of the DNA complex of the highly homologous zinc finger of GATA338 (PDB accession 3DFV). Mutated residues (magenta) are annotated and displayed with side chains. The mutations cluster at the DNA binding side of ZF1, suggesting they perturb DNA binding. Based on the homology model, N317, A318, L321, and R330 are directly implicated in DNA binding, so mutations in these residues probably alter the affinity to DNA or prevent DNA binding. G320 is important for proper attachment of an adjacent β-hairpin loop that provides additional DNA binding contacts. Q328 is not directly involved in DNA binding. However, Q328P could either affect the backbone fold of ZF1 and indirectly alter DNA binding by perturbing the adjacent R330, or alternatively is involved in interaction with other domains such as ZF2. All in all, the location of the mutations suggests that they influence DNA binding of ZF1.
