Structural and functional analysis of a novel proline-rich dimerisation/oligomerisation domain

蛋白质是由氨基酸组成的长链，是所有生物的基本组成部分。基因是DNA的片段，编码如何制造细胞所需的蛋白质的信息。这些信息由一组称为转录复合物的蛋白质解码，解码过程的第一步称为转录。为了确保由基因编码的信息仅在正确的情况下转录，有一组称为转录因子的蛋白质调节转录过程。转录因子是由大量的和可变数量的功能模块，使它们能够相互作用，与转录复合物和DNA。在转录因子和其他蛋白质中经常出现的一组模块富含脯氨酸。这些模块的特征在于存在大量脯氨酸残基。脯氨酸残基具有独特的结构，不能形成其他氨基酸之间发生的许多缔合。脯氨酸的不寻常结构的一个结果是，含有高密度脯氨酸残基的蛋白质以一种仅知之甚少的方式折叠成其三维形状（结构）。在转录因子中具有如此多富含脯氨酸的模块的原因以及这些模块的结构仅知之甚少。富含脯氨酸的同源结构域（PRH）蛋白是一种转录因子，其含有聚集在蛋白质的一个区域中的高密度脯氨酸残基。PRH是一种重要的蛋白质，它决定了细胞如何分裂，以及它们将来会变成什么样的细胞。PRH富含脯氨酸的区域对于调节基因转录和调节细胞分裂是重要的。我们目前的结果表明，PRH的富含脯氨酸的区域可以与DNA结合，也可以与其本身结合，形成包含2个PRH蛋白的称为二聚体的小复合物，或者形成包含许多PRH蛋白的称为低聚体的大复合物。我们想了解PRH中富含脯氨酸的序列如何影响整个PRH蛋白的二聚化和寡聚化。我们还想了解PRH利用富含脯氨酸的区域与自身和DNA结合的能力对于调节转录是否重要。由于其他与PRH功能类似的转录因子也具有类似的富含脯氨酸的序列，因此我们了解到的关于PRH的信息很可能适用于许多其他蛋白质。

Proteins are long chains of units called amino acids and are essential components of all living things. Genes are segments of DNA that encode information on how to make the proteins that are required by the cell. This information is decoded by a set of proteins known as the transcription complex and the first step in the decoding process is known as transcription. To ensure that the information encoded by a gene is only transcribed in the correct circumstances there are a group of proteins called transcription factors that regulate the transcription process. Transcription factors are made up of a large and variable number of functional modules that allow them to interact with each other, with the transcription complex and with DNA. One group of modules that occur frequently both in transcription factors and also in a variety of other proteins is proline-rich. These modules are characterised by the presence of a large number of proline residues. Proline residues have a unique structure that cannot form many of the associations that occur between the other amino acids. One consequence of the unusual structure of proline is that proteins that contain a high density of proline residues are folded into their three dimensional shape (structure) in a way that is only poorly understood. The reason for having so many proline-rich modules in transcription factors and the structure of these modules are only poorly understood. The Proline-Rich Homeodomain (PRH) protein is a transcription factor that contains a high density of proline residues clustered in one region of the protein. PRH is an important protein in determining how cells divide and what sort of cells they will become in the future. The proline-rich region of PRH is important for regulating the transcription of genes, and for regulating cell division. Our present results show that the proline-rich region of PRH can bind to DNA and also to itself either to form small complexes called dimers that contain 2 PRH proteins or large complexes called oligomers that contain many PRH proteins. We want to understand how the proline-rich sequence in PRH influences the dimerisation and oligomerisation of the entire PRH protein. We also want to understand whether the ability of the PRH to bind to itself and to DNA using the proline-rich region is important for regulating transcription. Since other transcription factors that function in a similar manner to PRH also have similar proline-rich sequences, the information that we learn about PRH is very likely to be applicable to many other proteins.