FINDING PROTEIN SEQUENCE MOTIFS--METHODS AND APPLICATIONS

基因组规模上蛋白质序列数据的生成在很大程度上 增加了对快速、灵敏和可靠的方法的需求 检测蛋白质中重要的保守基序(Cm)。一个 一种蛋白质序列数据库中CM的检测及评估方法 在履约协助方案中开发和实施了统计意义 (一致比对解析器)和MOST(基序搜索工具)程序。这个 大多数过程包括迭代地从对齐进行抽象 分块表示cm的权重矩阵，用以下方式扫描数据库 该矩阵，并定位要添加到对齐块的新段。 该方法的基础是分数分布的统计 位置相关的权重矩阵。此方法被推广为允许 使用两个以可变距离分隔的对齐块进行搜索；此 程序在MoST2程序中实现。母题的制作方法 检测进一步与蛋白质的其他方法结合使用 序列分析，以确定保守结构域和描绘 蛋白质超家族。这一策略被应用于各种 生物上重要的蛋白质群。精选实例：S-腺苷 真核核仁蛋白中发现了蛋氨酸结合基序 纤维蛋白，并预测纤维蛋白具有rRNA。 甲基转移酶活性。检测到一个二核苷酸结合区 在鸟嘌呤核苷酸交换蛋白家族中，其中之一是 与人类遗传性失明有关。一个蛋白质超家族 包含裂解酶结构域的结构域被描绘出来，并且出乎意料地，这样的结构域 在内收蛋白中检测到，内收蛋白是一种真核细胞骨架蛋白，与 遗传性高血压。一个核苷酸转移酶结构域，一个 乙酰基转移酶结构域和一种新的蛋白质-蛋白质相互作用 在一个真核翻译起始家族中检测到结构域 各种因素。蛋白质的保守基序文库 具有代表性的家族编码在大肠杆菌基因组中 建造的。图书馆由166个服务齐全的路线区块组成 它可以被MOST程序使用。该项目的意义 正在开发一种连贯的战略，以识别CM和 蛋白质超家族的结构域和划分及其在预测中的应用 一系列生物重要蛋白质的功能利用这些 方法：研究方法。

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.