Terenzi H, Alzari P M, Zakin M M
Unité d'Expression des Gènes Eucaryotes, Institut Pasteur, Paris, France.
Biochemistry. 1998 Aug 18;37(33):11488-95. doi: 10.1021/bi980748i.
The nuclear receptor superfamily comprises a group of transcriptional regulators involved in a wide variety of physiological responses. Rev-erb beta is a member of a growing subfamily of orphan nuclear receptors that bind DNA with high affinity either as monomers or as hetero- or homodimers. DNA bending assays, high-resolution footprinting, molecular modeling, and site-directed mutagenesis were used to analyze the structural features of the interaction between the DNA-binding domain (DBD) of the nuclear receptor Rev-erb beta and its DNA target sites. The results obtained point to the involvement of a carboxyl-terminal sequence adjacent to the second zinc finger of the Rev-erb beta DBD in protein-DNA interaction as a monomer or in protein-DNA and protein-protein interactions as a homodimer. They also provide insight about the amino acid residues directly involved in protein-protein contacts.
核受体超家族由一组参与多种生理反应的转录调节因子组成。Rev-erbβ是孤儿核受体中一个不断壮大的亚家族成员,它能以单体形式或作为异源或同源二聚体与DNA高亲和力结合。采用DNA弯曲分析、高分辨率足迹分析、分子建模和定点诱变等方法,分析核受体Rev-erbβ的DNA结合结构域(DBD)与其DNA靶位点之间相互作用的结构特征。所得结果表明,Rev-erbβ DBD第二个锌指附近的羧基末端序列参与了作为单体的蛋白质-DNA相互作用,以及作为同源二聚体的蛋白质-DNA和蛋白质-蛋白质相互作用。这些结果还为直接参与蛋白质-蛋白质相互作用的氨基酸残基提供了见解。