Structure is three to ten times more conserved than sequence-A study of structural response in protein cores
Structure is three to ten times more conserved than sequence-A study of structural response in protein cores
复制标题
DOI：
10.1002/prot.22458
复制
发表时间：
2009-11-15
影响因子：
2.9
通讯作者：
Elofison, Arne
中科院分区：
文献类型：
--
作者：
Illergard, Kristoffer;Ardell, David H.;Elofison, Arne
蛋白质结构在进化过程中因突变而发生变化。在这里，我们分析了一组结构对齐的蛋白质结构域中序列和结构之间的映射。为了避免伪影，我们将注意力限制在这些结构的核心组件上。我们发现，平均而言，使用不同的结构变化衡量标准，蛋白质核心随进化距离（每个位点的氨基酸取代）线性进化。无论我们使用哪种结构变化测量方法，无论是 RMSD 还是二级结构、可及性或接触的离散结构描述符，都是如此。这种线性响应使我们能够量化结构比序列更保守的说法。使用与序列字母表基数相似的结构字母表，结构核心的演化速度比序列慢三到十倍。尽管我们观察到平均线性响应，但我们发现了很大的方差。不同的领域家族对进化的结构反应有五倍的差异。试图按结构和功能类别对亚组之间的这种差异进行分类分析，只发现了一个统计上显着的趋势。这种趋势可以用以下事实来解释：β-折叠比α-螺旋变化得更快，很可能是因为它们更短并且变化发生在二级结构元件的末端。蛋白质2009； 77：499-508。 (C) 2009 Wiley-Liss, Inc.
Protein structures change during evolution in response to mutations. Here, we analyze the mapping between sequence and structure in a set of structurally aligned protein domains. To avoid artifacts, we restricted our attention only to the core components of these structures. We found that on average, using different measures of structural change, protein cores evolve linearly with evolutionary distance (amino acid substitutions per site). This is true irrespective of which measure of structural change we used, whether RMSD or discrete structural descriptors for secondary structure, accessibility, or contacts. This linear response allows us to quantify the claim that structure is more conserved than sequence. Using structural alphabets of similar cardinality to the sequence alphabet, structural cores evolve three to ten times slower than sequences. Although we observed an average linear response, we found a wide variance. Different domain families varied fivefold in structural response to evolution. An attempt to categorically analyze this variance among subgroups by structural and functional category revealed only one statistically significant trend. This trend can be explained by the fact that beta-sheets change faster than alpha-helices, most likely due to that they are shorter and that change occurs at the ends of the secondary structure elements. Proteins 2009; 77:499-508. (C) 2009 Wiley-Liss, Inc.