کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5371162 | 1503938 | 2013 | 8 صفحه PDF | دانلود رایگان |

Human ADAR1, which has two left-handed Z-DNA binding domains, preferentially binds Z-DNA rather than B-DNA with a high binding affinity. Z-DNA can be induced in long genomic DNA by Z-DNA binding proteins through the formation of two B-Z junctions with the extrusion of one base pair from each junction. We performed NMR experiments on complexes of ZαADAR1 with three DNA duplexes at a variety of protein-to-DNA molar ratios. This study confirmed that the ZαADAR1 first binds to an 8-bp CG-rich DNA segment via a unique conformation during B-Z transition and the neighboring AT-rich region becomes destabilized. We also found that, when DNA duplexes have only 6-bp CG-rich segment, the interaction with ZαADAR1 did not affect the thermal stabilities of the 6-bp CG-rich segment as well as the neighboring two A·T base pairs. These results indicate that four ZαADAR1 proteins interact with the 8-bp DNA sequence containing a 6-bp CG-repeat segment as well as a dinucleotide step, even though the dinucleotid step contains AâT base pairs. Thus this study suggests that the length of the CG-rich region is more important than the specific DNA sequence for determining which base-pair is extruded from the B-Z junction structure. This study also found that the ZαADAR1 in complex with a 11-bp DNA duplex exhibits a Z-DNA-bound conformation distinct from that of free ZαADAR1 and the initial contact conformations of ZαADAR1 complexed with 13-bp DNA duplexes.
Highlights⺠Zα binds to CG-rich DNA segment maintaining B-DNA via a unique conformation. ⺠Zα significantly destabilizes AâT base pairs outside 8-bp CG-rich region. ⺠Four ZαADAR1 protein monomers initially interact with the 8-bp DNA sequence, even though this segment contains AâT base pairs.
Journal: Biophysical Chemistry - Volume 172, February 2013, Pages 18-25