title: Structural propensities of human ubiquitination sites: accessibility, centrality and local conformation.
abstract: 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.
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
authors.forename: Sixue
authors.initials: S
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Jiangning
authors.initials: J
authors.lastname: Song
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
authors.forename: Ziding
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D006801:Humans; D020543:Proteome / Q000235:genetics* / Q000378:metabolism; D020539:Sequence Analysis, Protein; D013329:Structure-Activity Relationship; D054875:Ubiquitination / Q000235:genetics
chemical_list: D020543:Proteome