Identification of functional surfaces of the zinc binding domains of intracellular receptors
Identification of functional surfaces of the zinc binding domains of intracellular receptors
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DOI：
10.1006/jmbi.1997.1395
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发表时间：
1997-12-05
影响因子：
5.6
通讯作者：
Cohen, FE
中科院分区：
文献类型：
--
作者：
Lichtarge, O;Yamamoto, KR;Cohen, FE
转录调节因子复合物组装在基因组反应元件上以控制基因表达为了获得对决定来自细胞内受体的锌结合结构域中的这种组装的表面的见解，我们系统地分析了这些结构域在其不变折叠的背景下的序列和功能的变化。将细胞内受体超家族作为一个整体，揭示了与反应元件结合特异性相关的氨基酸残基沿着DNA界面的层次结构。当只考虑类固醇受体，两个额外的网站出现：已知的二聚体接口，和一个新的假定的接口适当地位于接触调节因子绑定到类固醇受体常用的回文反应元件的自由面。令人惊讶的是，视黄酸受体，不知道结合回文反应元件，包含这两个表面，这意味着它们可能在回文元件在某些情况下二聚化。这项工作将功能表面的进化痕迹分析扩展到蛋白质-DNA相互作用，表明痕量残基的协调交换如何可预测地切换结合特异性，并演示了如何检测仅从序列比较中不明显的功能表面。(C)出版社：Academic Press Limited。
Transcriptional regulatory factor complexes assemble on genomic response elements to control gene expression To gain insights on the surfaces that determine this assembly in the zinc binding domains from intracellular receptors, we systematically analyzed the variations in sequence and function of those domains in the context of their invariant fold. Taking the intracellular receptor superfamily as a whole revealed a hierarchy of amino acid residues along the DNA interface that correlated with response element binding specificity. When only steroid receptors were considered, two additional sites appeared: the known dimer interface, and a novel putative interface suitably located to contact regulatory factors bound to the free face of palindromic response elements commonly used by steroid receptors. Surprisingly, retinoic acid receptors, not known to bind palindromic response elements, contain both of these surfaces, implying that they may dimerize at palindromic elements under some circumstances. This work extends Evolutionary Trace analysis of functional surfaces to protein-DNA interactions, suggests how coordinated exchange of trace residues may predictably switch binding specificity, and demonstrates how to detect functional surfaces that are not apparent from sequence comparison alone. (C) 1997 Academic Press Limited.