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.

从多种细菌的基因序列推导出的蛋白质序列 古细菌，也越来越多地来自真核模型生物， 正在产生大量关于蛋白质功能、相互作用的新知识 和进化。 最初来自计算的新颖发现 序列和序列数据库的分析，已在 通过协调一致的方法与实验实验室合作 包括定向诱变和光谱/酶学分析。 正在开发计算策略来识别一些 涉及的功能性氨基酸序列模式，其中许多是 微妙而多变。 A. 参与 DNA 的蛋白质和蛋白质复合物 结合、诱变和修复。 对于已确定的 DNA 模式 结合区域，评估模式鉴别器的新方法是 正在开发并应用于更多新颖的模式。 低复杂度 序列在多亚基 DNA 结合的成分中很常见 复杂，需要在数据库搜索之前进行分析和过滤。 通过迭代采样自动局部多重比对的方法是 包括并基于各种类型 DNA 结合的测试集进行评估 主题。 B. 包括病原体在内的复杂细菌的序列家族。 来自病原菌的新序列的快速增长，以及 广泛多样化的原核生物，例如多细胞或分化 细菌、蓝细菌和古细菌，通过一系列研究 的计算分析。 超过50%的可分类 蛋白质序列在大肠杆菌和其他良好的蛋白质序列中没有对应物 研究了细菌，其中许多细菌具有真核同源物。 示例 低复杂性片段和多重重复正在出现 频率增加，尤其是涉及表面的蛋白质 相互作用，例如与免疫系统的相互作用，其中许多是进化的 迅速。 在其他情况下，新的化学和代谢功能已经 被发现了。 项目意义：基因组序列和蛋白质 代谢和形态发生多样性的结构研究 细菌和其他模式生物继续提供丰富且成本低廉的 分子功能和新发现的有效来源 蛋白质的进化，包括与人类疾病相关的方面。