Structural basis of RXR-DNA interactions

Structural basis of RXR-DNA interactions
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DOI:
10.1006/jmbi.1999.3457
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发表时间:
2000-02-18
影响因子:
5.6
通讯作者:
Rastinejad, F
Rastinejad, F
中科院分区:
生物学2区
文献类型:
--
作者:
Zhao, Q;Chasse, SA;Rastinejad, F

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9-顺式视黄酸受体RXR与DNA有效结合为同二聚体或异二聚体与其他核受体结合。这些RXR复合物的dna结合位点是一致序列的直接重复。中间间隔一到五个碱基对。在这里,我们报道了rxr -DNA结合域的2.1埃晶体结构,它作为一个同型二聚体与理想的直接重复DNA靶标复合物。该结构显示了基因调控位点如何诱导转录因子的构象变化,从而促进家庭-合作组装。具体来说,T-box中的α -螺旋被破坏以允许有效的dna结合和亚基二聚化。RXR表现出一种宽松的序列识别模式,每个六聚体半位点仅与三个碱基对相互作用。该结构说明了如何通过离散的蛋白质-蛋白质相互作用和串联DNA结合在这个大型真核转录因子家族中实现位点选择;具有特征间距的站点。(C) 2000年学术出版社。
The 9-cis retinoic acid receptor, RXR,binds DNA effectively as a homodimer or as a heterodimer with other nuclear receptors. The DNA-binding sites for these RXR complexes are direct repeats of a consensus sequence. separated by one to five base-pairs of intervening space. Here, we report the 2.1 Angstrom crystal structure df the RXR-DNA-binding domain as a homodimer in complex with its idealized direct repeat DNA target. The structure shows how a gene-regulatory site can induce conformational changes in a transcription factor that promote home-cooperative assembly. Specifically, an alpha-helix in the T-box is disrupted to allow efficient DNA-binding and subunit dimerization. RXR displays a relaxed mode of sequence recognition, interacting with only three base-pairs in each hexameric half-site. The structure illustrates how site selection is achieved in this large eukaryotic transcription factor family through discrete protein-protein interactions and the use of tandem DNA binding;sites with characteristic spacings. (C) 2000 Academic Press.