Zhou Yuan, Liu Sixue, Song Jiangning, Zhang Ziding
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
National Engineering Laboratory for Industrial Enzymes and Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China ; Department of Biochemistry and Molecular Biology, Faculty of Medicine, Monash University, Melbourne, Victoria, Australia.
PLoS One. 2013 Dec 11;8(12):e83167. doi: 10.1371/journal.pone.0083167. eCollection 2013.
The existence and function of most proteins in the human proteome are regulated by the ubiquitination process. To date, tens of thousands human ubiquitination sites have been identified from high-throughput proteomic studies. However, the mechanism of ubiquitination site selection remains elusive because of the complicated sequence pattern flanking the ubiquitination sites. In this study, we perform a systematic analysis of 1,330 ubiquitination sites in 505 protein structures and quantify the significantly high accessibility and unexpectedly high centrality of human ubiquitination sites. Further analysis suggests that the higher centrality of ubiquitination sites is associated with the multi-functionality of ubiquitination sites, among which protein-protein interaction sites are common targets of ubiquitination. Moreover, we demonstrate that ubiquitination sites are flanked by residues with non-random local conformation. Finally, we provide quantitative and unambiguous evidence that most of the structural propensities contain specific information about ubiquitination site selection that is not represented by the sequence pattern. Therefore, the hypothesis about the structural level of the ubiquitination site selection mechanism has been substantially approved.
人类蛋白质组中大多数蛋白质的存在和功能受泛素化过程调控。迄今为止，通过高通量蛋白质组学研究已鉴定出数万个泛素化位点。然而，由于泛素化位点两侧序列模式复杂，泛素化位点选择机制仍不清楚。在本研究中，我们对505个蛋白质结构中的1330个泛素化位点进行了系统分析，并量化了人类泛素化位点显著高的可及性和意外高的中心性。进一步分析表明，泛素化位点较高的中心性与泛素化位点的多功能性相关，其中蛋白质-蛋白质相互作用位点是泛素化的常见靶点。此外，我们证明泛素化位点两侧是具有非随机局部构象的残基。最后，我们提供了定量且明确的证据，表明大多数结构倾向包含有关泛素化位点选择的特定信息，而这些信息并非由序列模式所代表。因此，关于泛素化位点选择机制结构水平的假设已得到充分证实。
