Multiple co-evolutionary networks are supported by the common tertiary scaffold of the LacI/GalR proteins.
Multiple co-evolutionary networks are supported by the common tertiary scaffold of the LacI/GalR proteins.
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DOI：
10.1371/journal.pone.0084398
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Swint-Kruse L
中科院分区：
文献类型：
--
作者：
Parente DJ;Swint-Kruse L
蛋白质家族可能以两种方式在其共同的三级支架上进化出旁系同源功能。首先，功能重要位点的位置可能“硬连线”到结构中，通过改变这些位置的氨基酸（例如丙氨酸与丝氨酸）而进化出新的功能。或者，三级支架可能是适应性强的，为每个旁系同源功能容纳一组独特的功能上重要的位点。为了区分这些可能性，我们比较了 LacI/GalR 转录阻遏蛋白家族的六个最大旁系同源亚家族中的一组功能重要位点。 LacI/GalR 旁系同源物具有共同的三级结构，但序列同一性较低（≤30%），并调节多种代谢过程。通过保护和共同进化序列分析确定了功能上重要的位置。结果表明，保守位置混合使用了“硬连线”和“适应性”支架框架，但任何一对亚科之间的共同进化网络都非常不同。因此，三级结构可以容纳功能重要位置的多个网络。在设计和解释其他蛋白质家族的序列分析时应考虑这种可能性。实施保护和共同进化分析的软件可在 https://sourceforge.net/projects/coevolutils/ 上找到。
Protein families might evolve paralogous functions on their common tertiary scaffold in two ways. First, the locations of functionally-important sites might be “hard-wired” into the structure, with novel functions evolved by altering the amino acid (e.g. Ala vs Ser) at these positions. Alternatively, the tertiary scaffold might be adaptable, accommodating a unique set of functionally important sites for each paralogous function. To discriminate between these possibilities, we compared the set of functionally important sites in the six largest paralogous subfamilies of the LacI/GalR transcription repressor family. LacI/GalR paralogs share a common tertiary structure, but have low sequence identity (≤30%), and regulate a variety of metabolic processes. Functionally important positions were identified by conservation and co-evolutionary sequence analyses. Results showed that conserved positions use a mixture of the “hard-wired” and “accommodating” scaffold frameworks, but that the co-evolution networks were highly dissimilar between any pair of subfamilies. Therefore, the tertiary structure can accommodate multiple networks of functionally important positions. This possibility should be included when designing and interpreting sequence analyses of other protein families. Software implementing conservation and co-evolution analyses is available at https://sourceforge.net/projects/coevolutils/.
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