The solution structure of the Zalpha domain of the human RNA editing enzyme ADAR1 reveals a prepositioned binding surface for Z-DNA.
Double-stranded RNA deaminase I (ADAR1) contains the Z-DNA binding domain Zalpha. Here we report the solution structure of free Zalpha and map the interaction surface with Z-DNA, confirming roles previously assigned to residues by mutagenesis. Comparison with the crystal structure of the (Zalpha)(2)/Z-DNA complex shows that most Z-DNA contacting residues in free Zalpha are prepositioned to bind Z-DNA, thus minimizing the entropic cost of binding. Comparison with homologous (alpha+beta)helix-turn-helix/B-DNA complexes suggests that binding of Zalpha to B-DNA is disfavored by steric hindrance, but does not eliminate the possibility that related domains may bind to both B- and Z-DNA.
Schade
M
M
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Turner
C J
CJ
Kühne
R
R
Schmieder
P
P
Lowenhaupt
K
K
Herbert
A
A
Rich
A
A
Oschkinat
H
H
D000243:Adenosine Deaminase / Q000737:chemistry* / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D016601:RNA-Binding Proteins; D017386:Sequence Homology, Amino Acid; D012996:Solutions
D004268:DNA-Binding Proteins; D016601:RNA-Binding Proteins; D012996:Solutions; D004247:DNA; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase