Department of Molecular Biology, Laboratory for Molecular Infection Medicine Sweden, Umeå Centre for Microbial Research, Science for Life Laboratory, Umeå University, Umeå 901 87, Sweden.
Biosciences Institute, Newcastle University School of Medicine, Newcastle upon Tyne NE2 4HH, UK.
Mol Biol Evol. 2024 Jan 3;41(1). doi: 10.1093/molbev/msad254.
Ribosomes from different species can markedly differ in their composition by including dozens of ribosomal proteins that are unique to specific lineages but absent in others. However, it remains unknown how ribosomes acquire new proteins throughout evolution. Here, to help answer this question, we describe the evolution of the ribosomal protein msL1/msL2 that was recently found in ribosomes from the parasitic microorganism clade, microsporidia. We show that this protein has a conserved location in the ribosome but entirely dissimilar structures in different organisms: in each of the analyzed species, msL1/msL2 exhibits an altered secondary structure, an inverted orientation of the N-termini and C-termini on the ribosomal binding surface, and a completely transformed 3D fold. We then show that this fold switching is likely caused by changes in the ribosomal msL1/msL2-binding site, specifically, by variations in rRNA. These observations allow us to infer an evolutionary scenario in which a small, positively charged, de novo-born unfolded protein was first captured by rRNA to become part of the ribosome and subsequently underwent complete fold switching to optimize its binding to its evolving ribosomal binding site. Overall, our work provides a striking example of how a protein can switch its fold in the context of a complex biological assembly, while retaining its specificity for its molecular partner. This finding will help us better understand the origin and evolution of new protein components of complex molecular assemblies-thereby enhancing our ability to engineer biological molecules, identify protein homologs, and peer into the history of life on Earth.
核糖体在组成上可以有很大的差异，包含几十种核糖体蛋白，这些蛋白是特定谱系所特有的，而在其他谱系中则不存在。然而，目前尚不清楚核糖体在进化过程中是如何获得新的蛋白质的。在这里，为了帮助回答这个问题，我们描述了核糖体蛋白 msL1/msL2 的进化，该蛋白最近在寄生微生物类群微孢子虫的核糖体中被发现。我们表明，这种蛋白在核糖体中具有保守的位置，但在不同的生物体中具有完全不同的结构：在分析的每个物种中，msL1/msL2 都表现出改变的二级结构、N 末端和 C 末端在核糖体结合表面上的反转方向，以及完全转化的 3D 折叠。然后，我们表明这种折叠转换很可能是由核糖体 msL1/msL2 结合位点的变化引起的，特别是 rRNA 的变化。这些观察结果使我们能够推断出一个进化情景，其中一个小的、带正电荷的、新生成的未折叠蛋白首先被 rRNA 捕获，成为核糖体的一部分，随后经历完全的折叠转换，以优化其与不断进化的核糖体结合位点的结合。总的来说，我们的工作提供了一个引人注目的例子，说明蛋白质如何在复杂的生物组装的背景下改变其折叠，同时保持其对其分子伴侣的特异性。这一发现将帮助我们更好地理解复杂分子组装中新蛋白质成分的起源和进化，从而提高我们设计生物分子、识别蛋白质同源物以及深入了解地球生命历史的能力。
