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 Z alpha high affinity binding domain 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 other proteins with the potential for Z-DNA binding. We found that the tumor-associated protein DLM-1 contains a domain with remarkable sequence similarities to Z alpha(ADAR). Here we report the crystal structure of this DLM-1 domain bound to left-handed Z-DNA at 1.85 A resolution. Comparison of Z-DNA binding by DLM-1 and ADAR1 reveals a common structure-specific recognition core within the binding domain. However, the domains differ in certain residues peripheral to the protein-DNA interface. These structures reveal a general mechanism of Z-DNA recognition, suggesting the existence of a family of winged-helix proteins sharing a common Z-DNA binding motif.
Schwartz
T
T
Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Str. 10, D-13125 Berlin, Germany. Thomas.Schwartz@mail.rockefeller.edu
Behlke
J
J
Lowenhaupt
K
K
Heinemann
U
U
Rich
A
A
D000243:Adenosine Deaminase / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D006023:Glycoproteins / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins; D016415:Sequence Alignment; D014461:Ultracentrifugation
D004268:DNA-Binding Proteins; D006023:Glycoproteins; C498634:Igf2bp1 protein, rat; D016601:RNA-Binding Proteins; C402632:Zbp1 protein, mouse; D004247:DNA; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase