Evolutionary conservation of sequence motifs at sites of protein modification.
Evolutionary conservation of sequence motifs at sites of protein modification.
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DOI：
10.1016/j.jbc.2023.104617
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发表时间：
2023-05
影响因子：
4.8
通讯作者：
Dohlman, Henrik G.
中科院分区：
文献类型：
--
作者：
Li, Shuang;Dohlman, Henrik G.
基因复制在生物学中很常见，可能是功能多样化和专业化的重要来源。酿酒酵母在进化的早期经历了一次全基因组复制事件，并且保留了大量的复制基因。我们发现了超过3500种情况，其中两种旁系同源蛋白中只有一种经历翻译后修饰，尽管两者都保留了相同的氨基酸残基。我们还开发了一个基于Web的搜索算法（CoSMoS. c）。该研究基于1011个野生和驯化的酵母分离物对氨基酸序列的保守性进行评分，并将其用于比较不同修饰的旁系同源蛋白对。我们发现，最常见的修饰-磷酸化，泛素化，酰化，但不是N-糖基化-发生在高度序列保守的区域。这种保守性甚至对于泛素化和琥珀酰化也是明显的，其中没有确定的用于修饰的“共有位点”。磷酸化的差异与预测的二级结构或溶剂可及性无关，但反映了激酶-底物相互作用的已知差异。因此，翻译后修饰的差异可能是由于相邻氨基酸的差异及其与修饰酶的相互作用。通过整合来自大规模蛋白质组学和基因组学分析的数据，在一个具有如此丰富遗传多样性的系统中，我们对持续了1亿年的遗传冗余的功能基础有了更全面的了解。
Gene duplications are common in biology and are likely to be an important source of functional diversification and specialization. The yeast Saccharomyces cerevisiae underwent a whole-genome duplication event early in evolution, and a substantial number of duplicated genes have been retained. We identified more than 3500 instances where only one of two paralogous proteins undergoes posttranslational modification despite having retained the same amino acid residue in both. We also developed a web-based search algorithm (CoSMoS.c.) that scores conservation of amino acid sequences based on 1011 wild and domesticated yeast isolates and used it to compare differentially modified pairs of paralogous proteins. We found that the most common modifications—phosphorylation, ubiquitylation, and acylation but not N-glycosylation—occur in regions of high sequence conservation. Such conservation is evident even for ubiquitylation and succinylation, where there is no established ‘consensus site’ for modification. Differences in phosphorylation were not associated with predicted secondary structure or solvent accessibility but did mirror known differences in kinase–substrate interactions. Thus, differences in posttranslational modification likely result from differences in adjoining amino acids and their interactions with modifying enzymes. By integrating data from large-scale proteomics and genomics analysis, in a system with such substantial genetic diversity, we obtained a more comprehensive understanding of the functional basis for genetic redundancies that have persisted for 100 million years.
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影响因子：
3.7
作者：
Espinosa-Cantú A;Ascencio D;Barona-Gómez F;DeLuna A
通讯作者：
DeLuna A
影响因子：
6.4
作者：
Bradley, Patrick H.;Gibney, Patrick A.;Rabinowitz, Joshua D.
通讯作者：
Rabinowitz, Joshua D.
影响因子：
9.8
作者：
Conant GC;Wolfe KH
通讯作者：
Wolfe KH
影响因子：
4.5
作者：
Fares MA;Keane OM;Toft C;Carretero-Paulet L;Jones GW
通讯作者：
Jones GW
DOI：
10.1002/prot.340230412
发表时间：
1995-12-01
期刊：
PROTEINS-STRUCTURE FUNCTION AND GENETICS
影响因子：
--
作者：
Frishman, D;Argos, P
通讯作者：
Argos, P