FINDING PROTEIN SEQUENCE MOTIFS--METHODS AND APPLICATIONS

基因组规模上的蛋白质序列数据的产生极大地改变了基因组的结构。 增加了对快速、灵敏和可靠方法的需求， 检测蛋白质中功能重要的保守基序（CM）。 一 在蛋白质序列数据库中检测CM并评估其的方法 在CAP中开发并实施了统计学显著性 （一致性对齐解析器）和MoST（Motif搜索工具）程序。 的 大多数ST过程包括从比对中迭代提取 分块表示cm的权重矩阵，扫描数据库， 这个矩阵，并定位新的段添加到对齐块。 该方法是基于统计的分数分布， 位置相关权重矩阵。 这种方法被推广到允许 使用以可变距离分隔的两个对齐块进行搜索;此 在MoST2计划中实施了该程序。 Motif方法 检测还与其他蛋白质检测方法结合使用。 序列分析以鉴定保守结构域并描绘 蛋白质超家族 这一战略被应用于各种 生物学上重要的蛋白质组。 选择的实例：S-腺苷 在真核细胞核仁蛋白中发现了甲硫氨酸结合基序 原纤蛋白，并预测原纤蛋白具有rRNA 甲基转移酶活性。 检测到一个二核苷酸结合域 在鸟嘌呤核苷酸交换蛋白家族中， 与人类遗传性失明有关 蛋白质超家族 包含裂解酶结构域被描绘出来，出乎意料的是，这样的结构域 内收蛋白是一种真核细胞骨架蛋白， 遗传性高血压 核苷酸转移酶结构域， 乙酰转移酶结构域和一个假定的新的蛋白质-蛋白质相互作用 在真核生物翻译起始区的一个家族中检测到两个结构域 因素 一个表征蛋白质的保守基序库 大肠杆菌基因组编码的代表性家系， 构建了 图书馆由166个保存的校准块组成 可以被MOST计划使用。 项目的意义 正在制定一项连贯一致的战略， 结构域和描绘蛋白质超家族和预测 一些生物学上重要的蛋白质的功能 方法.

The generation of protein sequence data on a genome scale has greatly increased the demand for rapid, sensitive and reliable methods for detecting functionally important, conserved motifs (cm) in proteins. A method for detecting cm in protein sequence databases and assessing their statistical significance was developed and implemented in the CAP (Consistent Alignment Parser) and MoST (Motif Search Tool) programs. The MoST procedure consists of iteratively abstracting from an alignment block a weight matrix representing the cm, scanning the database with this matrix, and locating new segments to add to the alignment block. The approach is based on the statistics of score distributions for position-dependent weight matrices. This method was generalized to allow searches with two alignment blocks separated by a variable distance; this procedure was implemented in the MoST2 program. Methods for motif detection are further used in conjunction with other methods for protein sequence analysis in order to identify conserved domains and delineate protein superfamilies. This strategy was applied to a variety of biologically important groups of proteins. Selected examples: S-adenosyl methionine-binding motifs was identified in eukaryotic nucleolar proteins fibrillarins, and it was predicted that fibrillarins possess rRNA methyltransferase activity. A dinucleotide-binding domain was detected in a family of guanine nucleotide exchange proteins one of which is implicated in human hereditary blindness. A superfamily of proteins containing a lyase domain was delineated, and unexpectedly, such a domain was detected in adducin, a eukaryotic cytoskeletal protein implicated in hereditary hypertension. A nucleotidyltransferase domain, an acetyltransferase domain, and a putative new protein-protein interaction domain were detected in a family of eukaryotic translation initiation factors. A library of conserved motifs that characterize protein families with representatives encoded int he Escherichia coli genome was constructed. The library consists of 166 con-served alignment blocks that can be used by the MoST program. The significance of the project is in the development of a coherent strategy for identifying cm and domains and delineating protein superfamilies and in the prediction of the functions of a number of biologically important proteins using these methods.