SUBTLE SEQUENCE PATTERNS IN DNA-BINDING COMPLEXES

识别特定序列的蛋白质类别的数量和 DNA的结构继续快速增长。有几个是大的 几种亚基的复合体。在这个项目中，计算性 目前正在开发识别某些功能性氨基的策略 涉及到酸序列模式，其中许多是微妙和可变的。 改进的方法正被应用于新序列的分析 在NIH的其他实验室中确定的，导致了对 重要基因产物的分子结构和功能。为 已建立的DNA结合区的模式，如螺旋-转角-螺旋 和基本区域，评估诊断能力的新方法 模式鉴别器正在被开发并应用于更新颖的 模式。低复杂性序列在DNA结合蛋白中很常见 并且需要在数据库搜索之前进行分析和过滤。吉布斯一家 一种基于迭代采样的自动局部多重比对方法 也包括在这些战略中。各种类型的DNA的测试组- 为了评估这一点，我们已经明智地构建了结合主题 以及相关的方法。分析的特定序列包括：(1)127 kDa 紫外线损伤的DNA结合络合物的成分，在某些情况下是有缺陷的 E组色素性干皮病患者并显示出序列相似性 来自广泛的真核生物的未知功能的蛋白质，(2)六 转录因子TFIID复合体的亚基，在 通过促进启动子对不同基因的反应进行转录调控 激活剂，以及(3)各种DNA修复酶家族。

The number of classes of proteins that recognize specific sequences and structures of DNA is continuing to grow rapidly. Several are large complexes of several types of subunit. In this project, computational strategies are being developed to recognize some of the functional amino acid sequence patterns involved, many of which are subtle and variable. Improved methods are being applied to the analysis of new sequences determined in other NIH laboratories, resulting in new insights into the molecular structures and functions of important gene products. For patterns of well-established DNA binding regions such as helix-turn-helix and basic regions, new methods for evaluation of the diagnostic power of pattern discriminators are being developed and applied to more novel patterns. Low-complexity sequences are frequent in DNA-binding proteins and require analysis and filtering before database searches. The gibbs method of automated local multiple alignment by iterative sampling is also included in these strategies. Test sets of various types of DNA- binding motifs have been judiciously constructed for evaluation of this and related methods. Specific sequences analyzed include (1) 127 kDa component of a UV-damaged-DNA binding complex, which is defective in some Xeroderma pigmentosum Group E patients and shows sequence similarities to proteins of unknown function from a wide range of eukaryotes, (2) six subunits of the transcription factor TFIID complex that is central in transcriptional regulation by facilitating promoter responses to various activators, and (3) various families of DNA repair enzymes.