The effect of sequence evolution on protein structural divergence.

The effect of sequence evolution on protein structural divergence.
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序列进化对蛋白质结构差异的影响。

DOI:
10.1093/molbev/msp020
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发表时间:
2009
影响因子:
10.7
通讯作者:
Williams SG
Williams SG
中科院分区:
生物学1区
文献类型:
--
作者:
Williams SG

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由蛋白质结构和功能施加的复杂约束导致蛋白质中不同的序列和结构差异率。同源蛋白质之间的序列差异分析可以促进我们对结构差异的理解,以及对这些分子进化的一些限制。在这里,我们评估氨基酸序列和结构差异之间的关系。首先,我们证明了蛋白质序列和结构分歧之间的关系是由各种进化约束,包括溶剂暴露和二级结构。第二,虽然补偿性取代是普遍的,我们发现许多激进的大小变化的突变,不补偿相邻的互补变化。相反,这些非补偿取代通过改变蛋白质结构来减轻。这些结果表明,在蛋白质中的容纳取代的组合机制,涉及共同进化和结构的住宿。这样的机制可以解释先前观察到的相关取代的残基是遥远的序列和结构,允许一个综合的观点的序列和结构的差异蛋白质。
The complex constraints imposed by protein structure and function result in varied rates of sequence and structural divergence in proteins. Analysis of sequence differences between homologous proteins can advance our understanding of structural divergence and some of the constraints that govern the evolution of these molecules. Here, we assess the relationship between amino acid sequence and structural divergence. Firstly, we demonstrate that the relationship between protein sequence and structural divergence is governed by a variety of evolutionary constraints, including solvent exposure and secondary structure. Secondly, although compensatory substitutions are widespread, we find many radical size-changing mutations that are not compensated by neighboring complementary changes. Instead, these noncompensated substitutions are mitigated by alteration of protein structure. These results suggest a combined mechanism of accommodating substitutions in proteins, involving both coevolution and structural accommodation. Such a mechanism can explain previously observed correlated substitutions of residues that are distant both in sequence and structure, allowing an integrated view of sequence and structural divergence of proteins.
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