Correlation between posttranslational modification and intrinsic disorder in protein.

TL;DR: Analysis of NMR structures suggested disorder-to-order transitions might be introduced by modifications of phospho-serine/-threonine, mono-/di-/tri-methyllysine, sulfotyrosine, 4-carboxyglutamate, and potentially 4-hydroxyproline.

Abstract: Protein intrinsic disorder has been shown to play an important role in some posttranslational modifications (PTM). In this paper, we systematically investigated the correlation between protein disorder and dozens of PTMs using data from UniProt/Swiss-Prot and 3-D structures solved by NMR from Protein Data Bank. We observed that many PTMs have a preference for occurrence in disordered regions, including phospho-serine/-threonine/-tyrosine, hydroxylation, sulfotyrosine, S-geranylgeranyl cysteine, deamidated glutamine, 4-carboxyglutamate, 6'-bromotryptophan and most of methylation; while a few PTMs have a preference for occurrence in ordered regions, including 4-aspartylphosphate, S-nitrosocysteine, tele-methylhistidine, FMN conjugation, 4,5-dihydroxylysine, 3- methylthioaspartic acid, most of ADP-ribosylation, and most of FAD attachment. It is also noted that acetyllysine does not show any significant preference for occurrence in either disordered or ordered regions. Further analysis of NMR structures suggested disorder-toorder transitions might be introduced by modifications of phospho-serine/-threonine mono-/di-/tri-methyllysine, sulfotyrosine, 4-carboxyglutamate, and potentially 4-hydroxyproline. This study sheds light on the functions and mechanisms of various PTMs.