MOLECULAR NOVELTY AND CONSERVATION IN BACTERIAL PROTEIN SEQUENCES

细菌蛋白质序列的分子新颖性和保守性

• 批准号: 5203622
• 负责人: J WOOTTON
• 金额: --
• 依托单位: NATIONAL LIBRARY OF MEDICINE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5203622
• 关键词: DNA binding protein; automated data processing; bacterial proteins; biochemical evolution; computer assisted sequence analysis; computer program /software; computer system design /evaluation; method development; protein sequence; protein structure function

Protein sequences deduced from gene sequence of diverse bacteria and archaebacteria, and also, increasingly, from eukaryotic model organisms, are yielding a wealth of new knowledge on protein functions, interactions and evolution. Novel findings, that emerged initially from computational analysis of sequences and sequence database, have been studied in collaboration with experimental laboratories by concerted methods including directed mutagenesis and spectroscopic/enzymological analyses. Computational strategies are being developed to recognize some of the functional amino acid sequence patterns involved, many of which are subtle and variable. A. Proteins and protein complexes involved in DNA binding, mutagenesis and repair. For patterns of well-established DNA binding regions, new methods for evaluation of pattern discriminators are being developed and applied to more novel patterns. Low- complexity sequences are frequent in components of multisubunit DNA-binding complexes and require analysis and filtering before database searches. Methods of automated local multiple alignment by iterative sampling are included and evaluated based on test sets of various types of DNA-binding motifs. B. Sequence families in complex bacteria including pathogens. The rapidly growing body of new sequences from pathogenic bacteria, and widely diverse prokaryotes such as multicellular or differentiating bacteria, cyanobacteria and archaebacteria, were investigated by a range of computational analyses. More than 50 percent of the classifiable protein sequences did not have counterparts in E. coli and other well- studied bacteria, and many of these had eukaryotic homologs. Examples of low-complexity segments and multiple repeats are emerging with increasing frequency, especially in proteins involved in surface interactions, for example with the immune system, many of which evolve rapidly. In other cases, novel chemical and metabolic functions have been found. Significance of project: Genome sequences and protein structural studies from metabolically and morphogenetically diverse bacteria and other model organisms continue to provide a rich and cost- effective source of new discoveries on the molecular functions and evolution of proteins including aspects related to human diseases.

从不同细菌的基因序列推导的蛋白质序列和 古细菌，以及越来越多的真核模型生物， 在蛋白质功能，相互作用方面产生大量的新知识 和进化。 新发现，最初来自计算 序列和序列数据库的分析已在 通过协同方法与实验实验室合作 包括定向诱变和光谱/酶学分析。 正在制定计算策略以认识到一些 功能性氨基酸序列模式，其中许多是 微妙而可变。 A.参与DNA的蛋白质和蛋白质复合物 结合，诱变和修复。 对于已建立的DNA的模式 约束区域，评估模式歧视因子的新方法是 被开发并应用于更多新颖的模式。 低复杂性 序列在多亚基DNA结合的组件中很常见 复合物，需要在数据库搜索之前进行分析和过滤。 通过迭代采样的自动局部多重对齐方式的方法是 根据各种类型的DNA结合的测试集包括并评估 主题。 B.复杂细菌中的序列家族，包括病原体。 从致病细菌和 多样化的原核生物，例如多细胞或分化 细菌，蓝细菌和考古细菌，通过一个范围进行了研究 计算分析。 超过50％的分类 蛋白质序列没有大肠杆菌和其他良好的蛋白质序列 研究了细菌，其中许多具有真核同源物。 例子 低复杂性段和多次重复的段 频率增加，特别是在参与表面的蛋白质中 例如，与免疫系统相互作用，其中许多都在发展 迅速。 在其他情况下，新型的化学和代谢功能具有 被发现。 项目的重要性：基因组序列和蛋白质 来自代谢和形态学多样的结构研究 细菌和其他模型生物继续提供丰富的成本 - 关于分子功能的新发现的有效来源 蛋白质的进化，包括与人类疾病有关的方面。