Department of Molecular Biosciences, The University of Kansas, Lawrence, KS 66045, USA. Electronic address: https://twitter.com/Rik_Skywalker.
Department of Molecular Biosciences, The University of Kansas, Lawrence, KS 66045, USA.
J Mol Biol. 2023 Nov 15;435(22):168292. doi: 10.1016/j.jmb.2023.168292. Epub 2023 Sep 26.
In protein evolution, diversification is generally driven by genetic duplication. The hallmarks of this mechanism are visible in the repeating topology of various proteins. In outer membrane β-barrels, duplication is visible with β-hairpins as the repeating unit of the barrel. In contrast to the overall use of duplication in diversification, a computational study hypothesized evolutionary mechanisms other than hairpin duplications leading to increases in the number of strands in outer membrane β-barrels. Specifically, the topology of some 16- and 18-stranded β-barrels appear to have evolved through a loop to β-hairpin transition. Here we test this novel evolutionary mechanism by creating a chimeric protein from an 18-stranded β-barrel and an evolutionarily related 16-stranded β-barrel. The chimeric combination of the two was created by replacing loop L3 of the 16-stranded barrel with the sequentially matched transmembrane β-hairpin region of the 18-stranded barrel. We find the resulting chimeric protein is stable and has characteristics of increased strand number. This study provides the first experimental evidence supporting the evolution through a loop to β-hairpin transition.
在蛋白质进化中，多样化通常是由遗传复制驱动的。这种机制的特征在各种蛋白质的重复拓扑结构中可见。在外膜β-桶中，重复单元是β发夹，可见到复制。与多样化中普遍使用复制形成鲜明对比的是，一项计算研究假设了除发夹复制以外的其他进化机制，这些机制导致了外膜β-桶中链数的增加。具体来说，一些 16 股和 18 股β桶的拓扑结构似乎通过环到β发夹的转变而进化。在这里，我们通过从 18 股β桶和进化上相关的 16 股β桶创建嵌合蛋白来检验这种新的进化机制。通过用 18 股桶的顺序匹配的跨膜β发夹区域替换 16 股桶的环 L3 来创建两个桶的嵌合组合。我们发现所得的嵌合蛋白是稳定的，并且具有增加的链数的特征。这项研究提供了第一个实验证据，支持通过环到β发夹的转变进行进化。
