Structural And Functional Analysis Of Protein Sequence Families

蛋白质序列家族的结构和功能分析

基本信息

批准号：
7735069
负责人：
David LANDSMAN
金额：
$ 6.9万
依托单位：
NATIONAL LIBRARY OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

项目摘要

Several families of proteins are under investigation for the determination of the relationships between structure and function. Most of these protein families are eukaryotic nuclear proteins and have the property of binding to DNA or RNA, for example, the histone proteins, the HMG-1 box proteins, heat shock factors, ets proteins, HMG-I(Y) proteins, and ribosomal proteins. As an example, the HMG-1 box family of proteins is not highly conserved and is represented by over 100 examples in the sequence databases. We have identified a signature for this family of proteins and have classified them into several groups according to their sequence and functional relation. In the past few years, numerous proteins have been identified as containing a stretch of about 75 amino acids which are homologous to an abundant non-histone chromosomal protein HMG-1. These proteins bind DNA and bends it on binding or bind preferentially to bent DNA. Several of these proteins have been implicated in numerous nuclear functions including transcription, replication, and chromatin structure as well as transcription regulation in mitochondria resulting, in some cases, in such phenotypes as sex and mating type determination. For example, we have compiled a database of the HMG-1 box family of proteins and are analyzing the sequences to determine the phylogeny between these functionally widely-diverse proteins. The 3D structure of several HMG-1 box domains have been determined by multi-dimensional NMR. We have used one of these structure to model the other members of the family by a threading method. We have successfully produced models for the complete family of HMG-1 box domains. The conclusion drawn from these calculations is that these proteins are mostly likely to fold into similar conformations. An iterative motif search algorithm is being used to detect new and as yet unidentified motifs of several families of DNA-binding and RNA-binding proteins. In a separate project, we have identified several proteins which contain domains which could be related to the histone fold in the nucleosome octamer. We have identified conserved residues in all the histone proteins and related the conservation to the protein-protein and protein-DNA contact preservation in the histone folds in nucleosomes. We have developed and update the Histone Database for researchers to get curated sequence alignments of the histone proteins and histone fold containg proteins.

正在研究几个蛋白质家族以确定结构和功能之间的关系。这些蛋白质家族大多数是真核核蛋白，具有与 DNA 或 RNA 结合的特性，例如组蛋白、HMG-1 盒蛋白、热休克因子、ets 蛋白、HMG-I(Y) 蛋白和核糖体蛋白。例如，HMG-1 盒蛋白家族并不高度保守，在序列数据库中有 100 多个示例。我们已经确定了该蛋白质家族的特征，并根据其序列和功能关系将它们分为几组。在过去的几年中，许多蛋白质已被鉴定为含有一段约 75 个氨基酸，与丰富的非组蛋白染色体蛋白 HMG-1 同源。这些蛋白质结合 DNA 并在结合时使其弯曲或优先结合弯曲的 DNA。其中一些蛋白质与许多核功能有关，包括转录、复制和染色质结构以及线粒体中的转录调节，在某些情况下导致性别和交配类型确定等表型。例如，我们编制了 HMG-1 盒蛋白家族的数据库，并正在分析序列以确定这些功能广泛多样化的蛋白之间的系统发育。多个 HMG-1 盒结构域的 3D 结构已通过多维 NMR 确定。我们已经使用其中一个结构通过线程方法对该系列的其他成员进行建模。我们已经成功地为整个 HMG-1 盒子域系列制作了模型。从这些计算得出的结论是，这些蛋白质很可能折叠成相似的构象。迭代基序搜索算法被用来检测几个 DNA 结合和 RNA 结合蛋白家族的新的和尚未识别的基序。在一个单独的项目中，我们鉴定了几种蛋白质，它们含有可能与核小体八聚体中的组蛋白折叠相关的结构域。我们已经鉴定了所有组蛋白中的保守残基，并将这种保守性与核小体组蛋白折叠中的蛋白质-蛋白质和蛋白质-DNA 接触保存联系起来。我们开发并更新了组蛋白数据库，以便研究人员获得组蛋白和包含组蛋白折叠蛋白的精选序列比对。