Grütter M G, Weaver L H, Matthews B W
Nature. 1983 Jun 30;303(5920):828-31. doi: 10.1038/303828a0.
During evolution, the amino acid sequence of a protein is much more variable and changes more rapidly than its tertiary structure. Given sufficient time, the amino acid sequences of proteins derived from a common precursor may alter to the point that they are no longer demonstrably homologous. The ability to make meaningful comparisons between such distantly related proteins must therefore come primarily from structural homology, and only secondarily (if at all) from sequence homology. On the other hand, structural homology in the absence of sequence homology might be attributed to convergent rather than divergent evolution. (A common fold might be dictated by functional or folding requirements.) We have previously argued, on the basis of structural and functional similarities, that the lysozymes of hen egg-white and bacteriophage T4 have a common evolutionary precursor, even though their amino acid sequences have no detectable similarity. Here we report the structure of the lysozyme from Embden goose, a representative of a third class of lysozymes that has no sequence homology (or perhaps very weak homology) with either the hen egg-white or the phage enzyme. The structure of goose egg-white lysozyme has striking similarities to the lysozymes from hen egg-white and bacteriophage T4. However, some parts of goose lysozyme resemble hen lysozyme while other parts correspond only to the phage enzyme. The nature of the structural correspondence strongly suggests that all three lysozymes evolved from a common precursor.
在进化过程中,蛋白质的氨基酸序列比其三级结构更具变异性,变化也更快。如果有足够的时间,源自共同前体的蛋白质的氨基酸序列可能会改变到不再能明显显示出同源性的程度。因此,对这类远缘相关蛋白质进行有意义比较的能力主要必须来自结构同源性,其次(如果有的话)才来自序列同源性。另一方面,在没有序列同源性的情况下的结构同源性可能归因于趋同进化而非分歧进化。(一种常见的折叠方式可能由功能或折叠要求决定。)我们之前曾基于结构和功能的相似性提出,鸡蛋清溶菌酶和噬菌体T4溶菌酶有一个共同的进化前体,尽管它们的氨基酸序列没有可检测到的相似性。在此我们报道了来自恩登鹅的溶菌酶的结构,恩登鹅溶菌酶是第三类溶菌酶的代表,与鸡蛋清溶菌酶或噬菌体酶都没有序列同源性(或者可能只有非常弱的同源性)。鹅蛋清溶菌酶的结构与鸡蛋清溶菌酶和噬菌体T4溶菌酶有显著的相似性。然而,鹅溶菌酶的某些部分类似于鸡溶菌酶,而其他部分仅与噬菌体酶相对应。结构对应关系的性质强烈表明,所有这三种溶菌酶都从一个共同的前体进化而来。