Constraints and consequences of the emergence of amino acid repeats in eukaryotic proteins.
Constraints and consequences of the emergence of amino acid repeats in eukaryotic proteins.
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DOI：
10.1038/nsmb.3441
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发表时间：
2017-09
影响因子：
16.8
通讯作者：
Babu MM
中科院分区：
文献类型：
--
作者：
Chavali S;Chavali PL;Chalancon G;de Groot NS;Gemayel R;Latysheva NS;Ing-Simmons E;Verstrepen KJ;Balaji S;Babu MM
具有氨基酸同源序列的蛋白质具有对细胞有害的潜力，并且通常与人类疾病有关。那么，为什么同源重组在真核生物蛋白质组中普遍存在呢？在酵母中，我们发现homorepeats富含蛋白质，是必需的，多效性和缓冲环境的侮辱。它们的存在通过介导蛋白质相互作用并以重复依赖的方式促进空间组织来增加蛋白质的功能多样性。在进化过程中，homorepeats优先保留在严格的蛋白质稳定，这可能会减少重复相关的有害影响，如不受管制的相分离和蛋白质聚集的蛋白质。它们的存在通过氨基酸取代的积累促进了蛋白质的快速分化，这通常会影响线性基序和翻译后修饰位点。这可能导致重新连接蛋白质相互作用和信号网络。因此，homorepeats是不同的模块，通常保留在严格调控的蛋白质中。它们的存在有助于快速探索种群的基因型-表型景观，从而有助于适应性。
Proteins with amino acid homorepeats have the potential to be detrimental to cells and are often associated with human diseases. Why then are homorepeats prevalent in eukaryotic proteomes? In yeast, we find that homorepeats are enriched in proteins that are essential, pleiotropic and buffer environmental insults. Their presence increases functional versatility of proteins by mediating protein interactions and facilitating spatial organization in a repeat-dependent manner. During evolution, homorepeats are preferentially retained in proteins with stringent proteostasis, which might minimize repeat-associated detrimental effects such as unregulated phase separation and protein aggregation. Their presence facilitates rapid protein divergence through accumulation of amino acid substitutions, which often affect linear motifs and post-translational modification sites. This may result in rewiring protein interaction and signalling networks. Thus, homorepeats are distinct modules that are often retained in stringently regulated proteins. Their presence facilitates rapid exploration of the genotype-phenotype landscape of a population, thereby contributing to fitness.
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影响因子：
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作者：
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