MOLECULAR NOVELTY AND CONSERVATION IN BACTERIAL PROTEIN SEQUENCES

从不同细菌的基因序列推导的蛋白质序列， 古细菌，以及越来越多的真核模式生物， 产生了大量关于蛋白质功能，相互作用 和进化。 新的发现，最初出现在计算 序列分析和序列数据库，已在 通过协调一致的方法与实验室合作 包括定向诱变和光谱/酶学分析。 正在开发计算策略，以识别一些 功能氨基酸序列模式，其中许多是 微妙而多变。 a.与DNA有关的蛋白质和蛋白质复合物 结合、诱变和修复。 对于已经确定的DNA模式 结合区域，新的模式鉴别器的评价方法， 被开发并应用于更新颖的模式。 低复杂度 序列是多亚基DNA结合的组成部分， 复杂，需要在数据库搜索之前进行分析和过滤。 通过迭代采样进行自动局部多重比对的方法是 包括和评估的基础上测试集的各种类型的DNA结合 图案 B。包括病原体在内的复杂细菌中的序列家族。 来自病原菌的新序列的快速增长，以及 广泛多样的原核生物，如多细胞或分化 细菌，蓝藻和古细菌，进行了调查，由一系列 的计算分析。 超过50%的可分类 蛋白质序列在E.大肠杆菌和其他的 研究细菌，其中许多都有真核同源物。 示例 低复杂性片段和多个重复序列的出现， 增加频率，特别是在参与表面蛋白质 相互作用，例如与免疫系统的相互作用， 迅速 在其他情况下，新的化学和代谢功能， 项目意义：基因组序列和蛋白质 从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的和成本- 分子功能新发现的有效来源， 蛋白质的进化，包括与人类疾病有关的方面。

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.