Systematic functional prioritization of protein posttranslational modifications.
Systematic functional prioritization of protein posttranslational modifications.
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DOI：
10.1016/j.cell.2012.05.036
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发表时间：
2012-07-20
期刊：
影响因子：
64.5
通讯作者：
Krogan NJ
中科院分区：
文献类型：
--
作者：
Beltrao P;Albanèse V;Kenner LR;Swaney DL;Burlingame A;Villén J;Lim WA;Fraser JS;Frydman J;Krogan NJ
蛋白质功能通常由翻译后修饰（PTM）调节，质谱技术的最新进展导致PTM鉴定呈指数增长。然而，绝大多数这些修饰的功能意义仍然未知。为了解决这一问题，我们从11种真核生物中收集了近20万个磷酸化、乙酰化和泛素化位点，其中包括2500个新的酿酒酵母泛素化位点。我们开发了一些方法，通过预测那些可能参与交叉调节事件、调节结构域活性或介导蛋白质-蛋白质相互作用的ptm来优先考虑这些ptm的功能相关性。结构域家族内的PTM保护确定了与功能重要区域重叠的调控“热点”，我们在HSP70结构域家族上实验验证了这一概念。最后，我们对PTM调控进化的分析强调了调控相互作用中中性漂移的潜在途径，并表明只有一小部分修饰位点可能具有重要的生物学作用。
Protein function is often regulated by post-translational modifications (PTMs) and recent advances in mass-spectrometry have resulted in an exponential increase in PTM identification. However, the functional significance of the vast majority of these modifications remains unknown. To address this problem, we compiled nearly 200,000 phosphorylation, acetylation and ubiquitination sites from 11 eukaryotic species, including 2,500 novel ubiquitylation sites for S. cerevisiae. We developed methods to prioritize the functional relevance of these PTMs by predicting those that likely participate in cross-regulatory events, regulate domain activity or mediate protein-protein interactions. PTM conservation within domain families identifies regulatory ‘hot-spots’ that overlap with functionally important regions, a concept we experimentally validated on the HSP70 domain family. Finally, our analysis of the evolution of PTM regulation highlights potential routes for neutral drift in regulatory interactions and suggests that only a fraction of modification sites are likely to have a significant biological role.
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影响因子：
56.9
作者：
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通讯作者：
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影响因子：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
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发表时间：
2000-11-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
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作者：
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通讯作者：
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