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首页> 外文期刊>Journal of Molecular Biology >The dimerization/repression domain of RFX1 is related to a conserved region of its yeast homologues Crt1 and Sak1: a new function for an ancient motif.
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The dimerization/repression domain of RFX1 is related to a conserved region of its yeast homologues Crt1 and Sak1: a new function for an ancient motif.

机译：RFX1的二聚化/抑制域与其酵母同系物Crt1和Sak1的保守区有关：这是古老基序的新功能。

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摘要

The RFX protein family includes members from yeast to humans, which function in various biological systems, and share a DNA-binding domain and a conserved C-terminal region. In the human transcription regulator RFX1, the conserved C terminus is an independent functional domain, which mediates dimerization and transcriptional repression. This dimerization domain has a unique ability to mediate the formation of two alternative homodimeric DNA-protein complexes, the upper of which has been linked to repression. Here, we localize the complex formation capacity to several different RFX1 C-terminal subregions, each of which can function independently to generate the upper complex and repress transcription, thus correlating complex formation with repression. To gain an evolutionary perspective, we have examined whether the different properties of the RFX1 C terminus exist in the two yeast RFX proteins, which are involved in signaling pathways. Replacement of the RFX1 C terminus with those of Sak1 and Crt1, its orthologues from Schizosaccharomyces pombe and Saccharomyces cerevisiae, respectively, and analysis of fusions with the Gal4 DNA-binding domain, revealed that the ability to generate the two alternative complexes is conserved in the RFX family, from S. cerevisiae to man. While sharing this unique biochemical property, the three C termini differed from each other in their ability to mediate dimerization and transcriptional repression. In both functions, RFX1, Sak1, and Crt1 showed high capacity, moderate capacity, and no capacity, respectively. This comparative analysis of the RFX proteins, representing different evolutionary stages, suggests a gradual development of the conserved C terminus, from the appearance of the ancestral motif (Crt1), to the later acquisition of the dimerization/repression functions (Sak1), and finally to the enhancement of these functions to generate a domain mediating highly stable protein-protein interactions and potent transcriptional repression (RFX1). Copyright 1999 Academic Press.
机译：RFX蛋白家族包括从酵母到人类的成员，它们在各种生物系统中发挥作用，并共享一个DNA结合域和一个保守的C端区域。在人类转录调节因子RFX1中，保守的C末端是一个独立的功能域，介导二聚化和转录抑制。该二聚化结构域具有介导两种替代的同型二聚体DNA-蛋白质复合物形成的独特能力，其上部与抑制作用有关。在这里，我们将复合物的形成能力定位于几个不同的RFX1 C末端亚区域，每个子区域都可以独立发挥作用以生成上部复合物并抑制转录，从而将复合物的形成与抑制相关联。为了获得进化的观点，我们检查了两个信号通路中涉及的酵母RFX蛋白中是否存在RFX1 C末端的不同特性。用Sak1和Crt1取代RFX1 C末端，分别来自粟酒裂殖酵母和酿酒酵母的直向同源物，并分析与Gal4 DNA结合结构域的融合物，发现生成两种替代复合物的能力是保守的。 RFX家族，从酿酒酵母到人。在共享这种独特的生化特性的同时，三个C末端在介导二聚化和转录抑制方面的能力也有所不同。在这两个功能中，RFX1，Sak1和Crt1分别显示高容量，中等容量和无容量。代表不同进化阶段的RFX蛋白质的这种比较分析表明，从祖先基序（Crt1）的出现到后来的二聚化/阻遏功能（Sak1）的获得，保守C末端的逐渐发展增强这些功能以产生介导高度稳定的蛋白质-蛋白质相互作用和有效转录抑制（RFX1）的域。版权所有1999，学术出版社。

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