Molecular Endocrinology Laboratory, Department Molecular Cell Biology, Campus GHB, ON1, Herestraat 49, 3000 Leuven, Belgium.
Mol Cell Endocrinol. 2012 Jan 30;348(2):411-7. doi: 10.1016/j.mce.2011.07.025. Epub 2011 Jul 27.
The gene family of nuclear receptors is characterized by the presence of a typical, well conserved DNA-binding domain. In general, two zinc coordinating modules are folded such that an α-helix is inserted in the major groove of the DNA-helix displaying a sequence similar to one of two hexameric consensus motifs. Both zinc molecules coordinate four cysteines. Although the DNA-binding domains as well as the hormone response elements are very similar, each nuclear receptor will affect transcription of a specific set of target genes. This is in part due to some important receptor-specific variations on the general theme of DNA interaction. For most nuclear receptors, the DNA-binding domain dimerizes on DNA, which explains why most hormone response elements consist of a repeat of two hexamers. The hexamer dimers can be organized either as direct, inverted or everted repeats with spacers of varying lengths. The DNA can be bound by homodimers, heterodimers and for some orphan receptors, as monomer. Another key element for DNA binding by nuclear receptors is the carboxy-terminal extension of the DNA-binding domain extending into the hinge region. This part not only co-determines sequence specificity, but also affects other functions of the receptors like nuclear translocation, intranuclear mobility and transactivation potential. Moreover, allosteric signals passing through towards other receptor domains, explain why to some extent, the DNA elements can also be considered as controlling ligands.
核受体的基因家族的特征是存在典型的、高度保守的 DNA 结合结构域。通常，两个锌配位模块折叠，使得一个α螺旋插入 DNA-螺旋的大沟中，展示出与两个六聚体共识基序之一相似的序列。两个锌分子都与四个半胱氨酸配位。尽管 DNA 结合结构域和激素反应元件非常相似，但每个核受体都会影响特定一组靶基因的转录。这部分是由于 DNA 相互作用的一般主题上存在一些重要的受体特异性变化。对于大多数核受体，DNA 结合结构域在 DNA 上二聚化，这解释了为什么大多数激素反应元件由两个六聚体重复组成。六聚体二聚体可以组织成直接、倒置或反转重复，具有不同长度的间隔。DNA 可以由同源二聚体、异源二聚体和一些孤儿受体结合成单体。核受体 DNA 结合的另一个关键要素是 DNA 结合结构域的羧基末端延伸到铰链区。这部分不仅共同决定了序列特异性，还影响受体的其他功能，如核易位、核内迁移性和转录激活潜力。此外，通过其他受体结构域传递的变构信号，解释了为什么在某种程度上，DNA 元件也可以被认为是控制配体。
