NF-κB p52:RelB heterodimer recognizes two classes of κB sites with two distinct modes
NF-κB p52:RelB heterodimer recognizes two classes of κB sites with two distinct modes
复制标题
DOI：
10.1038/embor.2008.227
复制
发表时间：
2009-02-01
期刊：
影响因子：
7.7
通讯作者：
Ghosh, Gourisankar
中科院分区：
文献类型：
--
作者：
Fusco, Amanda J.;Huang, De-Bin;Ghosh, Gourisankar
核因子-κ B（NF-κ B）p52：RelB：κ B DNA复合物的X射线结构揭示了一种以前在其他NF-κ B：κ B DNA复合物中未见的新识别特征。RelB的Arg 125与另外的DNA碱基对接触。令人惊讶的是，P52：RelB R125 A突变体异二聚体仅对κ B位点的亚类显示DNA结合和转录活性的缺陷。我们发现，精氨酸125敏感的κ B网站包含更多的连续和位于中心的A：T碱基对比不敏感的网站。在该复合物中观察到的蛋白质诱导的扭结（使用富含AT的κ B位点）可能允许Arg 125与DNA接触;在具有非富含AT的κ B位点的复合物中，这种扭结可能是不可能的。此外，我们表明，p52：RelB B异二聚体结合更广泛的kappa B网站相比，p50：RelA异二聚体。我们认为p52：RelB异源二聚体与其他NF-κ B二聚体相比，更能适应κ B位点的互补序列和结构变异。
The X-ray structure of the nuclear factor-kappa B (NF-kappa B) p52:RelB:kappa B DNA complex reveals a new recognition feature not previously seen in other NF-kappa B:kappa B DNA complexes. Arg 125 of RelB is in contact with an additional DNA base pair. Surprisingly, the p52: RelB R125A mutant heterodimer shows defects both in DNA binding and in transcriptional activity only to a subclass of kappa B sites. We found that the Arg 125-sensitive kappa B sites contain more contiguous and centrally located A:T base pairs than do the insensitive sites. A protein-induced kink observed in this complex, which used an AT-rich kappa B site, might allow the DNA contact by Arg 125; such a kink might not be possible in complexes with non-AT-rich kappa B sites. Furthermore, we show that the p52: RelB heterodimer binds to a broader spectrum of kappa B sites when compared with the p50:RelA heterodimer. We suggest that the p52: RelB heterodimer is more adaptable to complement sequence and structural variations in kappa B sites when compared with other NF-kappa B dimers.