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首页> 外文期刊>Molecular and Cellular Biology >Structural and Functional Analysis of Mutations along the Crystallographic Dimer Interface of the Yeast TATA Binding Protein
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Structural and Functional Analysis of Mutations along the Crystallographic Dimer Interface of the Yeast TATA Binding Protein

机译：沿酵母TATA结合蛋白的结晶二聚体界面突变的结构和功能分析

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The TATA binding protein (TBP) is a central component of the eukaryotic transcription machinery and is subjected to both positive and negative regulation. As is evident from structural and functional studies, TBP's concave DNA binding surface is inhibited by a number of potential mechanisms, including homodimerization and binding to the TAND domain of the TFIID subunit TAF1 (yTAFII145/130). Here we further characterized these interactions by creating mutations at 24 amino acids within the Saccharomyces cerevisiae TBP crystallographic dimer interface. These mutants are impaired for dimerization, TAF1 TAND binding, and TATA binding to an extent that is consistent with the crystal or nuclear magnetic resonance structure of these or related interactions. In vivo, these mutants displayed a variety of phenotypes, the severity of which correlated with relative dimer instability in vitro. The phenotypes included a low steady-state level of the mutant TBP, transcriptional derepression, dominant slow growth (partial toxicity), and synthetic toxicity in combination with a deletion of the TAF1 TAND domain. These phenotypes cannot be accounted for by defective interactions with other known TBP inhibitors and likely reflect defects in TBP dimerization.
机译：TATA结合蛋白（TBP）是真核转录机制的重要组成部分，并受到正向和负向调节。从结构和功能研究中可以明显看出，TBP的凹形DNA结合表面受到多种潜在机制的抑制，包括同二聚化和与TFIID亚基TAF1（yTAF II 145/130）的TAND域结合。 。在这里，我们通过在啤酒酵母TBP晶体学二聚体界面内的24个氨基酸处产生突变来进一步表征这些相互作用。这些突变体的二聚化，TAF1 TAND结合和TATA结合受损的程度与这些相互作用或相关相互作用的晶体或核磁共振结构一致。在体内，这些突变体表现出多种表型，其表型与体外相对二聚体不稳定性相关。这些表型包括突变体TBP的低稳态水平，转录抑制，显性缓慢生长（部分毒性）和合成毒性以及TAF1 TAND结构域的缺失。这些表型不能由与其他已知TBP抑制剂的相互作用不良来解释，并且很可能反映了TBP二聚化中的缺陷。

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