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

蛋白质是由称为氨基酸的单位组成的长链，是所有生物的重要组成部分。基因是DNA的片段，它编码有关如何制造细胞所需蛋白质的信息。这种信息由一组被称为转录复合体的蛋白质解码，解码过程的第一步被称为转录。为了确保基因编码的信息只在正确的环境下转录，有一组被称为转录因子的蛋白质调节转录过程。转录因子由大量可变数量的功能模块组成，这些功能模块允许它们相互作用，与转录复合体和DNA相互作用。在转录因子和各种其他蛋白质中频繁出现的一组模块是富含脯氨酸的。这些模块的特点是存在大量的脯氨酸残基。脯氨酸残基有一种独特的结构，不能形成其他氨基酸之间的许多联系。Pro这种不寻常结构的一个后果是，含有高密度Pro残基的蛋白质以一种鲜为人知的方式被折叠成其三维形状(结构)。为什么转录因子中有这么多富含脯氨酸的模块，以及这些模块的结构，人们还知之甚少。富含Pro同源结构域(PRH)的蛋白质是一种转录因子，它含有聚集在蛋白质某一区域的高密度的Pro残基。PRH是一种重要的蛋白质，决定了细胞如何分裂以及未来它们将成为什么样的细胞。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Pro的区域可以与DNA结合，也可以与自身结合，形成包含2个PRH蛋白的称为二聚体的小复合体，或者形成包含许多PRH蛋白的称为寡聚体的大复合体。我们想了解PRH中富含Pro的序列是如何影响整个PRH蛋白的二聚化和寡聚化的。我们还想了解PRH与自身结合的能力以及利用富含Pro的区域与DNA结合的能力是否对调控转录是重要的。由于与PRH功能相似的其他转录因子也有类似的富含脯氨酸的序列，我们所了解的关于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.