کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5371162 1503938 2013 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
NMR investigation on the DNA binding and B-Z transition pathway of the Zα domain of human ADAR1
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی تئوریک و عملی
پیش نمایش صفحه اول مقاله
NMR investigation on the DNA binding and B-Z transition pathway of the Zα domain of human ADAR1
چکیده انگلیسی

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 A∙T 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► Zα binds to CG-rich DNA segment maintaining B-DNA via a unique conformation. ► Zα significantly destabilizes A∙T base pairs outside 8-bp CG-rich region. ► Four ZαADAR1 protein monomers initially interact with the 8-bp DNA sequence, even though this segment contains A∙T base pairs.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biophysical Chemistry - Volume 172, February 2013, Pages 18-25
نویسندگان
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