FINDING PROTEIN SEQUENCE MOTIFS--METHODS AND APPLICATIONS

在过去的几年中，基因组序列和蛋白质结构的快速积累与序列数据库搜索方法的重大进展是并行的。NCBI开发的功能强大的位置特异性迭代BLAST （PSI-BLAST）方法为我们的蛋白质基序分析工作奠定了基础。开发了一种新的PSI-BLAST应用模式，该模式包括通过重复PSI-BLAST迭代来穷尽数据库搜索以收敛新鉴定的蛋白质家族成员，并在自动过程中实现。另一个新的程序，IMPALA，是PSI-BLAST方法的反转，允许人们通过使用单个蛋白质序列作为查询来搜索蛋白质家族谱库。这些方法被应用于几种蛋白质结构域的系统分析。研究表明，一些以前被认为是真核生物特异性的信号域在古细菌和/或细菌中是可检测到的。结合结构域检测和跨基因组比较，将这些结构域分为祖先结构域和水平转移结构域。详细研究了构成修复系统和细胞程序性死亡系统的蛋白质结构域的进化历史。此外，对古细菌基因组中编码的dna结合结构域进行了深入的研究，结果表明，古细菌中的这些结构域与细菌中的相似，而与真核生物中的不同。许多以前未被发现的结构域和蛋白质家族被发现，包括ACT结构域参与多种酶的变构调节的多用途配体结合模型，以及来自细菌，古细菌和真核生物的预测蛋白酶的超家族，这些超家族与动物转谷氨酰胺酶同源。-蛋白质序列基序，迭代数据库搜索，折叠识别，多重比对

In the last few years, rapid accumulation of genome sequences and protein structures has been paralleled by major advances in sequence database search methods. The powerful Position-Specific Iterating BLAST (PSI-BLAST) method developed at the NCBI formed the basis of our work on protein motif analysis. A new mode of PSI-BLAST application which includes exhaustive database search by repeating PSI-BLAST iterations to convergence with newly identified protein family members was developed and implemented in an automatic procedure. Another new procedure, IMPALA, is a reversal of the PSI-BLAST method and allows one to search a library of protein family profiles by using an individual protein sequence as a query. These methods were applied to the systematic analysis of several classes of protein domains. It was shown that a number of signaling domains previously considered to be specifically eukaryotic are detectable in archaea and/or bacteria. By combining domain detection with a cross-genome comparison, these domains were classified into ancestral and horizontally transferred ones. The evolutionary histories of protein domains that comprise the repair systems and programmed cell death systems were investigated in detail. Also, the DNA-binding domains encoded in archaeal genomes have been thoroughly studied resulting in the demonstration that the repertoire of such domains in archaea resembles that in bacteria but not in eukaryotes. A number of previously undetected domains and protein families were discovered including the ACT domain  multipurpose ligand-binding model involved in allosteric regulation of avariety of enzymes and a superfamily of predicted protease from bacteria, archaea and eukaryotes that are homologous to animal transglutaminases. - Protein sequence motifs, iterative database search, fold recognition, multiple alignment