Heinz D W, Baase W A, Dahlquist F W, Matthews B W
Institute of Molecular Biology, University of Oregon, Eugene 97403.
Nature. 1993 Feb 11;361(6412):561-4. doi: 10.1038/361561a0.
Studies of extant protein sequences indicate that amino-acid insertions and deletions are preferentially located in loop regions, which has traditionally been explained as the result of selection removing deleterious mutations within secondary structural elements from the population. But there is no a priori reason to discount the possibility that insertions within secondary structure could either be tolerated until compensatory mutations arise, or have effects that are propagated away from secondary structure into loops. Earlier studies have indicated that insertions are generally tolerated, although much less well within secondary structure elements than in loop regions. Here we show that amino-acid insertions in an alpha-helix of T4 lysozyme can be accepted in two different ways. In some cases the inserted amino acids are accommodated within the helix, leading to the translocation of wild-type residues from the helix to the preceding loop. In other cases the insertion causes a 'looping-out' in the first or last turn of the helix. The individual structural responses seem to be dominated by the maintenance of the interface between the helix and the rest of the protein.
对现存蛋白质序列的研究表明，氨基酸插入和缺失优先发生在环区，传统上这被解释为选择作用从群体中去除二级结构元件内有害突变的结果。但是，没有先验理由排除二级结构内的插入可能在补偿性突变出现之前被容忍，或者具有从二级结构传播到环区的效应的可能性。早期研究表明，插入通常是可以容忍的，尽管在二级结构元件内比在环区的容忍程度要低得多。在这里，我们表明T4溶菌酶α螺旋中的氨基酸插入可以通过两种不同方式被接受。在某些情况下，插入的氨基酸被容纳在螺旋内，导致野生型残基从螺旋转移到前面的环区。在其他情况下，插入会导致螺旋第一圈或最后一圈出现“环出”。个体结构反应似乎主要由螺旋与蛋白质其余部分之间界面的维持所主导。
