Caffrey D R, O'Neill L A, Shields D C
Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, Dublin.
Protein Sci. 2000 Apr;9(4):655-70. doi: 10.1110/ps.9.4.655.
Physicochemical properties are potentially useful in predicting functional differences between aligned protein subfamilies. We present a method that considers physicochemical properties from ancestral sequences predicted to have given rise to the subfamilies of interest by gene duplication. Comparison between two map kinases subfamilies, p38 and ERK, revealed a region that had an excess of change in properties after gene duplication followed by conservation within the two subfamilies. This region corresponded to that experimentally defined as important for substrate and pathway specificity. The derived scores for the region of interest were found to differ significantly in their distribution compared to the rest of the protein when the Kolmogorov-Smirnov test was applied (p = 0.005). Thus, the incorporation of ancestral physicochemical properties is useful in predicting functional differences between protein subfamilies. In addition, the method was applied to the MKK and MAPK components of the p38 and JNK pathways. These proteins showed a similar pattern in their evolution and regions predicted to confer functional differences are discussed.
物理化学性质在预测比对后的蛋白质亚家族之间的功能差异方面可能很有用。我们提出了一种方法，该方法考虑了通过基因复制产生感兴趣的亚家族的祖先序列的物理化学性质。对两个丝裂原活化蛋白激酶亚家族p38和ERK的比较显示，在基因复制后有一个性质变化过多的区域，随后在这两个亚家族中保守。该区域对应于实验确定的对底物和途径特异性很重要的区域。当应用柯尔莫哥洛夫-斯米尔诺夫检验时，发现感兴趣区域的推导分数在分布上与蛋白质的其余部分有显著差异（p = 0.005）。因此，纳入祖先的物理化学性质有助于预测蛋白质亚家族之间的功能差异。此外，该方法应用于p38和JNK途径的MKK和MAPK组分。这些蛋白质在其进化中表现出相似的模式，并讨论了预测赋予功能差异的区域。
