Towards understanding the crosstalk between protein post-translational modifications: Homo- and heterotypic PTM pair distances on protein surfaces are not random
Towards understanding the crosstalk between protein post-translational modifications: Homo- and heterotypic PTM pair distances on protein surfaces are not random
复制标题
DOI：
10.1002/prot.25200
复制
发表时间：
2017-01-01
影响因子：
2.9
通讯作者：
Walther, Dirk
中科院分区：
文献类型：
--
作者：
Korkuc, Paula;Walther, Dirk
翻译后修饰（ptm）是影响蛋白质结构和功能的重要调控层。随着不同PTM类型发生的实验信息的广泛可用性，不同PTM类型之间的潜在串扰及其组合效应的研究已成为研究的重点。假设不同PTM类型和位点之间的相关干扰可能在调查它们相互的物理距离时变得明显，我们考虑到它们在蛋白质结构中的序列和空间距离，对7种常见PTM类型的人型和异型距离进行了系统的调查。我们发现实际的PTM位点距离分布与随机分布不同，除了同型磷酸化位点距离和磷酸化位点与泛素化位点之间的距离被发现比偶然的预期更近外，大多数PTM类型对的距离都比预期的要大。与任何氨基酸残基类型之间的距离相比，仅考虑典型受体氨基酸残基的随机参考分布被发现转移到更大的距离，这表明ptm可适应残基类型的潜在趋势比随机预期的更远。基于序列分离的距离分布与空间对应的距离分布基本一致，这表明基于序列的成对ptm位置编码的主要作用，而不是折叠介导的作用。我们的分析提供了一个系统和全面的概述蛋白质上成对PTM位点距离的特征，并揭示，主要是PTM位点倾向于避免接近，这可能意味着PTM的独立附着或去除仍然是可能的。蛋白质2016;85:78 - 92。(c) 2016 Wiley Periodicals, Inc.；
Post-translational modifications (PTMs) represent an important regulatory layer influencing the structure and function of proteins. With broader availability of experimental information on the occurrences of different PTM types, the investigation of a potential crosstalk between different PTM types and combinatorial effects have moved into the research focus. Hypothesizing that relevant interferences between different PTM types and sites may become apparent when investigating their mutual physical distances, we performed a systematic survey of pairwise homo- and heterotypic distances of seven frequent PTM types considering their sequence and spatial distances in resolved protein structures. We found that actual PTM site distance distributions differ from random distributions with most PTM type pairs exhibiting larger than expected distances with the exception of homotypic phosphorylation site distances and distances between phosphorylation and ubiquitination sites that were found to be closer than expected by chance. Random reference distributions considering canonical acceptor amino acid residues only were found to be shifted to larger distances compared to distances between any amino acid residue type indicating an underlying tendency of PTM-amenable residue types to be further apart than randomly expected. Distance distributions based on sequence separations were found largely consistent with their spatial counterparts suggesting a primary role of sequence-based pairwise PTM-location encoding rather than folding-mediated effects. Our analysis provides a systematic and comprehensive overview of the characteristics of pairwise PTM site distances on proteins and reveals that, predominantly, PTM sites tend to avoid close proximity with the potential implication that an independent attachment or removal of PTMs remains possible. Proteins 2016; 85:78-92. (c) 2016 Wiley Periodicals, Inc.