Mahajan Swapnil, de Brevern Alexandre G, Offmann Bernard, Srinivasan Narayanaswamy
a Faculté des Sciences et Technologies, Université de La Réunion , F-97715 Saint Denis Messag Cedex 09, La Réunion , France .
J Biomol Struct Dyn. 2014;32(5):751-8. doi: 10.1080/07391102.2013.789989. Epub 2013 Jun 3.
Conformational changes in proteins are extremely important for their biochemical functions. Correlation between inherent conformational variations in a protein and conformational differences in its homologues of known structure is still unclear. In this study, we have used a structural alphabet called Protein Blocks (PBs). PBs are used to perform abstraction of protein 3-D structures into a 1-D strings of 16 alphabets (a-p) based on dihedral angles of overlapping pentapeptides. We have analyzed the variations in local conformations in terms of PBs represented in the ensembles of 801 protein structures determined using NMR spectroscopy. In the analysis of concatenated data over all the residues in all the NMR ensembles, we observe that the overall nature of inherent local structural variations in NMR ensembles is similar to the nature of local structural differences in homologous proteins with a high correlation coefficient of .94. High correlation at the alignment positions corresponding to helical and β-sheet regions is only expected. However, the correlation coefficient by considering only the loop regions is also quite high (.91). Surprisingly, segregated position-wise analysis shows that this high correlation does not hold true to loop regions at the structurally equivalent positions in NMR ensembles and their homologues of known structure. This suggests that the general nature of local structural changes is unique; however most of the local structural variations in loop regions of NMR ensembles do not correlate to their local structural differences at structurally equivalent positions in homologues.
蛋白质的构象变化对其生化功能极为重要。蛋白质固有的构象变化与其已知结构的同源物中的构象差异之间的相关性仍不清楚。在本研究中，我们使用了一种称为蛋白质模块（PBs）的结构字母表。PBs用于基于重叠五肽的二面角将蛋白质三维结构抽象为16个字母（a - p）的一维字符串。我们根据使用核磁共振光谱法测定的801个蛋白质结构集合中表示的PBs分析了局部构象的变化。在对所有核磁共振集合中所有残基的连接数据进行分析时，我们观察到核磁共振集合中固有局部结构变化的总体性质与同源蛋白质中局部结构差异的性质相似，相关系数高达0.94。仅在对应于螺旋和β折叠区域的比对位置处预期有高相关性。然而，仅考虑环区域时的相关系数也相当高（0.91）。令人惊讶的是，按位置分离分析表明，这种高相关性在核磁共振集合及其已知结构的同源物中结构等效位置的环区域并不成立。这表明局部结构变化的一般性质是独特的；然而，核磁共振集合环区域中的大多数局部结构变化与其同源物中结构等效位置处的局部结构差异不相关。
