Evolutionary optimization of protein folding.
Evolutionary optimization of protein folding.
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DOI：
10.1371/journal.pcbi.1002861
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发表时间：
2013
影响因子：
4.3
通讯作者：
Gräter F
中科院分区：
文献类型：
--
作者：
Debès C;Wang M;Caetano-Anollés G;Gräter F
自38亿年前蛋白质出现以来，大自然就塑造了蛋白质的组成。然而，导致蛋白质异常多样性的结构变化的基本驱动因素尚未阐明。在这里，我们探索蛋白质进化是否影响折叠速度。我们估计折叠时间的蛋白质结构域直接从他们的大小修改的接触顺序，目前的目录。这些值被映射到一个进化的时间轴的域的外观来自于一个蛋白质结构域在989个完全测序的基因组的基因组分析。我们的研究结果表明，在进化过程中，折叠速度明显整体增加，已知的超快下坡文件夹出现在时间轴的后期。值得注意的是，折叠优化取决于二级结构。虽然α-折叠在整个进化过程中表现出折叠速度更快的趋势，但β-折叠在过去15亿年中表现出折叠时间增加的趋势，这是在结构域组合的“大爆炸”期间开始的。因此，这些域结构今天平均是缓慢的文件夹。我们的研究结果表明，结构域的快速和有效折叠塑造了蛋白质结构的宇宙。这一发现支持了这样的假设，即优化天然折叠的动力学和热力学可及性降低了阻碍细胞功能的蛋白质聚集倾向。大自然已经提出了各种各样的蛋白质三维结构，其中每一种都被认为是针对其特定功能进行优化的。一个基本的生物学奋进是揭示发现和优化新折叠的驱动进化力量。一个长期存在的假设是，折叠进化服从约束，以正确折叠成天然结构。在这里，我们通过分析蛋白质在进化过程中快速折叠的趋势来验证这一假设。利用基因组和结构分析，我们观察到38亿至15亿年前折叠时间的总体减少，这可以解释为快速折叠的进化优化。这种快速折叠的趋势可能导致多方面的优势，包括细胞的高蛋白质可及性和错误折叠期间蛋白质聚集的减少。
Nature has shaped the make up of proteins since their appearance, 3.8 billion years ago. However, the fundamental drivers of structural change responsible for the extraordinary diversity of proteins have yet to be elucidated. Here we explore if protein evolution affects folding speed. We estimated folding times for the present-day catalog of protein domains directly from their size-modified contact order. These values were mapped onto an evolutionary timeline of domain appearance derived from a phylogenomic analysis of protein domains in 989 fully-sequenced genomes. Our results show a clear overall increase of folding speed during evolution, with known ultra-fast downhill folders appearing rather late in the timeline. Remarkably, folding optimization depends on secondary structure. While alpha-folds showed a tendency to fold faster throughout evolution, beta-folds exhibited a trend of folding time increase during the last 1.5 billion years that began during the “big bang” of domain combinations. As a consequence, these domain structures are on average slow folders today. Our results suggest that fast and efficient folding of domains shaped the universe of protein structure. This finding supports the hypothesis that optimization of the kinetic and thermodynamic accessibility of the native fold reduces protein aggregation propensities that hamper cellular functions. Nature has come up with an enormous variety of protein three-dimensional structures, each of which is thought to be optimized for its specific function. A fundamental biological endeavor is to uncover the driving evolutionary forces for discovering and optimizing new folds. A long-standing hypothesis is that fold evolution obeys constraints to properly fold into native structure. We here test this hypothesis by analyzing trends of proteins to fold fast during evolution. Using phylogenomic and structural analyses, we observe an overall decrease in folding times between 3.8 and 1.5 billion years ago, which can be interpreted as an evolutionary optimization for rapid folding. This trend towards fast folding probably resulted in manifold advantages, including high protein accessibility for the cell and a reduction of protein aggregation during misfolding.
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Bogatyreva, Natalya S.;Osypov, Alexander A.;Ivankov, Dmitry N.
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