Protein evolution speed depends on its stability and abundance and on chaperone concentrations.-猫眼课题宝

DOI：

10.1073/pnas.1810194115

发表时间：

2018-09-11

期刊：

Proceedings of the National Academy of Sciences of the United States of America

影响因子：

11.1

通讯作者：

中科院分区：

综合性期刊1区

文献类型：

作者：

Agozzino L;Dill KA

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140491/

有些生物进化很慢(数百万年)，有些生物进化很快(几个月到几年)。蛋白质进化的速度取决于蛋白质的折叠结构有多稳定，它避免聚集的能力有多强，以及它的陪伴能力有多强。其机制是什么？我们通过将蛋白质折叠平衡模型与序列变化动力学相结合来计算适应度景观。我们发现，对于折叠最不稳定的蛋白质来说，适应新环境的速度最快，因为这些蛋白质位于健康潜力的陡峭下坡部分。该模型表明，细胞应该比较冷的环境更快地适应温暖的环境，解释了为什么增加蛋白质的丰度会减缓细胞的进化，并解释了伴侣如何通过减轻这种影响来加速进化。蛋白质以不同的速度进化。是什么推动了蛋白质序列变化的速度？两个主要因素是蛋白质的折叠稳定性和聚集倾向。通过将疏水-极性(HP)模型与Zwanzig-Szabo-Bagchi速率理论相结合，我们发现：(I)选择压力强烈地加速了适应，解释了生物体适应新环境的时间从几天到数千年的广泛差异。(Ii)适应最快的蛋白质是那些折叠不太稳定的蛋白质，因为它们的适应范围最陡峭。由于加热会破坏折叠蛋白质的稳定性，我们预测，当细胞处于较温暖的环境而不是较冷的环境时，会更快地适应。(Iii)蛋白质丰度的增加会减缓进化(序列的替换率)，因为典型的蛋白质并不是完全匹配的，因此增加其拷贝数会降低细胞的适应性。然而，伴侣可以通过有效地增强蛋白质的稳定性来缓解这种丰度效应并加速进化(也称为进化电容)。这个模型解释了关于蛋白质进化速度的关键观察结果。

Some biological evolution is slow (millions of years), and some is fast (months to years). The speed at which a protein evolves depends on how stable a protein’s folded structure is, how well it avoids aggregation, and how well-chaperoned it is. What are the mechanisms? We compute fitness landscapes by combining a model of protein-folding equilibria with sequence-change dynamics. We find that adapting to a new environment is fastest for proteins that are least stably folded, because those sit on steep downhill parts of fitness potentials. The modeling shows that cells should adapt to warmer environments faster than to colder ones, explains why increasing a protein’s abundance slows cell evolution, and explains how chaperones accelerate evolution by mitigating this effect. Proteins evolve at different rates. What drives the speed of protein sequence changes? Two main factors are a protein’s folding stability and aggregation propensity. By combining the hydrophobic–polar (HP) model with the Zwanzig–Szabo–Bagchi rate theory, we find that: (i) Adaptation is strongly accelerated by selection pressure, explaining the broad variation from days to thousands of years over which organisms adapt to new environments. (ii) The proteins that adapt fastest are those that are not very stably folded, because their fitness landscapes are steepest. And because heating destabilizes folded proteins, we predict that cells should adapt faster when put into warmer rather than cooler environments. (iii) Increasing protein abundance slows down evolution (the substitution rate of the sequence) because a typical protein is not perfectly fit, so increasing its number of copies reduces the cell’s fitness. (iv) However, chaperones can mitigate this abundance effect and accelerate evolution (also called evolutionary capacitance) by effectively enhancing protein stability. This model explains key observations about protein evolution rates.