Cellular crowding imposes global constraints on the chemistry and evolution of proteomes
Cellular crowding imposes global constraints on the chemistry and evolution of proteomes
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DOI：
10.1073/pnas.1209312109
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发表时间：
2012-12-11
影响因子：
11.1
通讯作者：
Teichmann, Sarah A.
中科院分区：
文献类型：
--
作者：
Levy, Emmanuel D.;De, Subhajyoti;Teichmann, Sarah A.
在活细胞中，功能性蛋白-蛋白相互作用与大量非功能性或混杂的相互作用相互竞争。一些细胞特性有助于避免不必要的蛋白质相互作用，包括基因表达的调节，细胞区隔化，以及功能性相互作用的高特异性和亲和力。在这里，我们研究是否存在其他机制来塑造蛋白质的序列和结构，以有利于它们正确组装成功能性蛋白质复合物。为了研究这个问题，我们将进化和细胞丰度信息分别投射到大肠杆菌、酿酒酵母和智人的397、196和631种已知3D结构的蛋白质上。根据界面斑块中的氨基酸频率与溶剂可接近的蛋白质表面的氨基酸频率，我们定义了20种氨基酸中的每种氨基酸的倾向或“粘性”尺度。我们发现以非特异性方式相互作用的倾向与丰度呈负相关。换句话说，高丰度的蛋白质具有较少粘性的表面。我们还发现黏性限制了蛋白质的进化，因此黏性表面斑块中的残基比非黏性斑块中的残基更保守。最后，我们发现黏性对蛋白质发散的约束与蛋白质丰度成正比，这为蛋白质守恒与蛋白质丰度之间的关系提供了机制见解。总的来说，避免非功能性相互作用显著地影响了蛋白质的物理化学和进化特性。值得注意的是，观察到的影响在大肠杆菌和酿酒杆菌中始终比在智人中更大，这表明在人类谱系中，混杂的蛋白质-蛋白质相互作用可能更容易积累。
In living cells, functional protein-protein interactions compete with a much larger number of nonfunctional, or promiscuous, interactions. Several cellular properties contribute to avoiding unwanted protein interactions, including regulation of gene expression, cellular compartmentalization, and high specificity and affinity of functional interactions. Here we investigate whether other mechanisms exist that shape the sequence and structure of proteins to favor their correct assembly into functional protein complexes. To examine this question, we project evolutionary and cellular abundance information onto 397, 196, and 631 proteins of known 3D structure from Escherichia coli, Saccharomyces cerevisiae, and Homo sapiens, respectively. On the basis of amino acid frequencies in interface patches versus the solvent-accessible protein surface, we define a propensity or "stickiness" scale for each of the 20 amino acids. We find that the propensity to interact in a nonspecific manner is inversely correlated with abundance. In other words, high abundance proteins have less sticky surfaces. We also find that stickiness constrains protein evolution, whereby residues in sticky surface patches are more conserved than those found in nonsticky patches. Finally, we find that the constraint imposed by stickiness on protein divergence is proportional to protein abundance, which provides mechanistic insights into the correlation between protein conservation and protein abundance. Overall, the avoidance of nonfunctional interactions significantly influences the physico-chemical and evolutionary properties of proteins. Remarkably, the effects observed are consistently larger in E. coli and S. cerevisiae than in H. sapiens, suggesting that promiscuous protein-protein interactions may be freer to accumulate in the human lineage.