A 6 bp Z-DNA hairpin binds two Z alpha domains from the human RNA editing enzyme ADAR1.
The Z alpha domain of the human RNA editing enzyme double-stranded RNA deaminase I (ADAR1) binds to left-handed Z-DNA with high affinity. We found by analytical ultracentrifugation and CD spectroscopy that two Z alpha domains bind to one d(CG)3T4(CG)3 hairpin which contains a stem of six base pairs in the Z-DNA conformation. Both wild-type Z alpha and a C125S mutant show a mean dissociation constant of 30 nM as measured by surface plasmon resonance and analytical ultracentrifugation. Our data suggest that short (> or = 6 bp) segments of Z-DNA within a gene are able to recruit two ADAR1 enzymes to that particular site.
Schade
M
M
Department of Biology, Massachusetts Institute of Technology (MIT), Cambridge 02139, USA.
Behlke
J
J
Lowenhaupt
K
K
Herbert
A
A
Rich
A
A
Oschkinat
H
H
D000243:Adenosine Deaminase / Q000235:genetics* / Q000378:metabolism*; D001665:Binding Sites; D002942:Circular Dichroism; D004247:DNA / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D016296:Mutagenesis; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D017393:RNA Editing; D016601:RNA-Binding Proteins; D013997:Time Factors; D014461:Ultracentrifugation
D016601:RNA-Binding Proteins; D004247:DNA; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase