首页> 外文期刊>Molecular and Cellular Biology >The orphan receptors NGFI-B and steroidogenic factor 1 establish monomer binding as a third paradigm of nuclear receptor-DNA interaction.
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The orphan receptors NGFI-B and steroidogenic factor 1 establish monomer binding as a third paradigm of nuclear receptor-DNA interaction.

机译:孤儿受体NGFI-B和类固醇生成因子1建立单体结合,这是核受体与DNA相互作用的第三个范式。

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We examined in detail the DNA interaction of the nuclear receptors NGFI-B and steroidogenic factor 1 (SF-1) by using a series of gain-of-function domain swaps. NGFI-B bound with high affinity as a monomer to a nearly linear DNA molecule. The prototypic zinc modules interacted with a half-site of the estrogen receptor class, and a distinct protein motif carboxy terminal to the zinc modules (the A box) interacted with two A/T base pairs 5' to the half-site. SF-1 bound in the same manner as NGFI-B, with an overlapping but distinct sequence requirement 5' to the half-site. The key features that distinguished the NGFI-B and SF-1 interactions were an amino group in the minor groove of the SF-1 binding sequence and an asparagine in the SF-1 A box. These results define a common mechanism of NGFI-B and SF-1 DNA binding, which may underlie a competitive mechanism of gene regulation in steroidogenic tissues that express these proteins. This monomer-DNA interaction represents a third paradigm of DNA binding by nuclear receptors in addition to direct and inverted dimerization.
机译:我们通过使用一系列功能获得的域交换,详细检查了核受体NGFI-B和类固醇生成因子1(SF-1)的DNA相互作用。 NGFI-B以高亲和力作为单体与几乎线性的DNA分子结合。原型锌模块与雌激素受体类别的一个半位相互作用,并且锌模块(A框)的一个独特的蛋白质基序羧基末端与两个半位的A / T碱基对5'相互作用。 SF-1以与NGFI-B相同的方式结合,其中半位点有5个重叠但不同的序列要求。区分NGFI-B和SF-1相互作用的关键特征是SF-1结合序列小沟中的氨基和SF-1 A盒中的天冬酰胺。这些结果定义了NGFI-B和SF-1 DNA结合的共同机制,这可能是表达这些蛋白质的类固醇生成组织中基因调节竞争机制的基础。除了直接和反向二聚作用外,这种单体与DNA的相互作用代表了核受体与DNA结合的第三种范式。

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