Sequence and hydropathy profile analysis of two classes of secondary transporters
Sequence and hydropathy profile analysis of two classes of secondary transporters
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DOI：
10.1080/09687860500063324
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发表时间：
2005-05-01
影响因子：
--
通讯作者：
Slotboom, DJ
中科院分区：
文献类型：
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作者：
Lolkema, JS;Slotboom, DJ
膜蛋白MemGen分类中的一个结构类是一组具有相似全局折叠的进化相关蛋白。一个结构类既包含亲缘关系较近的蛋白质对（通过序列比较可以清楚地看出同源性），也包含亲缘关系较远的蛋白质对（仅通过序列相似性无法确定同源性）。在后一种情况下，进化联系是基于亲水剖面分析。在这里，我们使用这些进化相关的蛋白质集来分析BLAST搜索中的e值、多序列比对中的序列相似性以及亲水剖面分析中的结构相似性之间的关系。二级转运蛋白有两种结构类型，称为ST[3]，其中包括离子转运蛋白（IT）超家族和ST[4]，其中包括DAACS家族（tc# 2.A）。23)从NCBI蛋白数据库中提取。ST[3]包含2051个独特序列，分布在32个科和59个亚科。ST[4]是一个较小的类，包含399个独特序列，分布在2个科和7个亚科中。ST[4]的一个亚家族包含一类新的依赖结合蛋白的二级转运蛋白。比较ST[3]和ST[4]亚科的平均亲水剖面，发现这两个亚科代表不同的褶皱。在ST[4]中所观察到的序列差异要比在ST[3]中所观察到的小得多，这表明在进化过程中对蛋白质的限制不同。对一类蛋白对的进化关系与BLAST e值的相关性分析表明：(i) BLAST算法无法提取结构类ST[3]中蛋白质之间的大多数联系，（ii）“低复杂度过滤”和“基于成分的统计”提高了特异性，但大大降低了BLAST搜索远亲蛋白质的敏感性，表明这些过滤器对所分析的蛋白质过于严格，以及（iii） e值截止值。可用于评估BLAST搜索中命中的进化意义的方法对于膜蛋白的两种结构类别是非常不同的。
A structural class in the MemGen classification of membrane proteins is a set of evolutionary related proteins sharing a similar global fold. A structural class contains both closely related pairs of proteins for which homology is clear from sequence comparison and very distantly related pairs, for which it is not possible to establish homology based on sequence similarity alone. In the latter case the evolutionary link is based on hydropathy profile analysis. Here, we use these evolutionary related sets of proteins to analyze the relationship between E-values in BLAST searches, sequence similarities in multiple sequence alignments and structural similarities in hydropathy profile analyses. Two structural classes of secondary transporters termed ST[3], which includes the Ion Transporter ( IT) superfamily and ST[ 4], which includes the DAACS family (TC# 2.A.23) were extracted from the NCBI protein database. ST[ 3] contains 2051 unique sequences distributed over 32 families and 59 subfamilies. ST[ 4] is a smaller class containing 399 unique sequences distributed over 2 families and 7 subfamilies. One subfamily in ST[ 4] contains a new class of binding protein dependent secondary transporters. Comparison of the averaged hydropathy profiles of the subfamilies in ST[ 3] and ST[ 4] revealed that the two classes represent different folds. Divergence of the sequences in ST[ 4] is much smaller than observed in ST[ 3], suggesting different constraints on the proteins during evolution. Analysis of the correlation between the evolutionary relationship of pairs of proteins in a class and the BLAST E-value revealed that: (i) the BLAST algorithm is unable to pick up the majority of the links between proteins in structural class ST[ 3], (ii) 'low complexity filtering' and 'composition based statistics' improve the specificity, but strongly reduce the sensitivity of BLAST searches for distantly related proteins, indicating that these filters are too stringent for the proteins analyzed, and (iii) the E-value cut-off, which may be used to evaluate evolutionary significance of a hit in a BLAST search is very different for the two structural classes of membrane proteins.