What the protein data bank tells us about the evolutionary conservation of protein conformational diversity.
What the protein data bank tells us about the evolutionary conservation of protein conformational diversity.
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蛋白质数据库告诉我们关于蛋白质构象多样性的进化保守性。
DOI：
10.1002/pro.4325
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发表时间：
2022-07
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
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作者：
蛋白质通过经历小规模和大规模的构象变化来采样多种不同的构象，这些构象变化通常是其功能所固有的。关于这些变化的信息通常被捕获在蛋白质数据库中，这是通过相同蛋白质的独立结构解决方案的明显冗余沉积来实现的。在这里，我们挖掘这些数据来研究同源蛋白质之间大规模构象变化的保守性。这对于实际原因（例如通过比较建模预测蛋白质的替代构象）和概念原因（例如理解进化中不同特征的保守程度）都很重要。为了研究这个问题，我们引入了一种新的方法，通过比较蛋白质之间的差异距离图（DDM）来比较蛋白质之间的构象变化。我们发现，经历类似构象变化的蛋白质具有相似的DDM，并且这种相似性可以通过DDM之间的相关性来量化。通过比较同源蛋白质对的DDM，我们发现大规模的构象变化在广泛的序列同一性中显示出高水平的保守性。这表明，构象空间通常是保守的同系物之间，即使是相对遥远的。
Proteins sample a multitude of different conformations by undergoing small‐ and large‐scale conformational changes that are often intrinsic to their functions. Information about these changes is often captured in the Protein Data Bank by the apparently redundant deposition of independent structural solutions of identical proteins. Here, we mine these data to examine the conservation of large‐scale conformational changes between homologous proteins. This is important for both practical reasons, such as predicting alternative conformations of a protein by comparative modeling, and conceptual reasons, such as understanding the extent of conservation of different features in evolution. To study this question, we introduce a novel approach to compare conformational changes between proteins by the comparison of their difference distance maps (DDMs). We found that proteins undergoing similar conformational changes have similar DDMs and that this similarity could be quantified by the correlation between the DDMs. By comparing the DDMs of homologous protein pairs, we found that large‐scale conformational changes show a high level of conservation across a broad range of sequence identities. This shows that conformational space is usually conserved between homologs, even relatively distant ones.
影响因子：
5.6
作者：
Sedova M;Jaroszewski L;Iyer M;Li Z;Godzik A
通讯作者：
Godzik A