Structure of the DLM-1-Z-DNA complex reveals a conserved family of Z-DNA-binding proteins

The first crystal structure of a protein, the Zu high affinity binding doma in of the RNA editing enzyme ADAR1, bound to left-handed Z-DNA was recently described. The essential set of residues determined from this structure to be critical for Z-DNA recognition was used to search the database for othe r proteins,with the potential for Z-DNA binding. We found that the tumor-as sociated protein DLM-1 contains a domain with remarkable sequence similarit ies to Z alpha (ADAR). Here we report the crystal structure of this DLM-1 d omain bound to left-handed Z-DNA at 1.85 Angstrom resolution. Comparison of Z-DNA binding by DLM-1 and ADAR1 reveals a common structure-specific-recog nition core within the binding domain. However, the domains differ in certa in residues peripheral to the protein-DNA interface. These structures revea l a general mechanism of Z-DNA recognition, suggesting the existence of a f amily of winged-helix proteins sharing a common Z-DNA binding motif.