Human Proteins with Target Sites of Multiple Post-Translational Modification Types Are More Prone to Be Involved in Disease
Publication in refereed journal


摘要Many proteins can be modified by multiple types of post. translational modifications (Mtp-proteins). Although some post-translational modifications (PTMs) have recently been found to be associated with life-threatening diseases like cancers and neurodegenerative disorders, the underlying mechanisms remain enigmatic to date. In this study, we examined the relationship of human Mtp-proteins and disease and systematically characterized features of these proteins. Our results indicated that Mtp-proteins are significantly more inclined to participate in disease than proteins carrying no known PTM sites. Mtp-proteins were found significantly enriched in protein complexes, having more protein partners and preferred to act as hubs/superhubs in protein protein interaction (PPI) networks. They possess a distinct functional focus, such as chromatin assembly or disassembly, and reside in biased, multiple subcellular localizations. Moreover, most Mtp-proteins harbor more intrinsically disordered regions than the others. Mtp-proteins carrying PTM types biased toward locating in the ordered regions were mainly related to protein DNA complex assembly. Examination of the energetic effects of PTMs on the stability of PPI revealed that only a small fraction of single PTM events influence the binding energy of >2 kcal/mol, whereas the binding energy can change dramatically by combinations of multiple PTM types. Our work not only expands the understanding of Mtp-proteins but also discloses the potential ability of Mtp-proteins to act as key elements in disease development.
著者Huang QL, Chang JH, Cheung MK, Nong WY, Li L, Lee MT, Kwan HS
期刊名稱Journal of Proteome Research
頁次2735 - 2748
關鍵詞disease development; intrinsically disordered region; post-translational modification; protein-protein interaction; topological coefficient
Web of Science 學科類別Biochemical Research Methods; BIOCHEMICAL RESEARCH METHODS; Biochemistry & Molecular Biology

上次更新時間 2020-24-10 於 02:24