Investigation of the impact of PTMs on the protein backbone conformation.

Abstract

Post-translational modifications (PTMs) are known to play a critical role in the regulation of protein functions. Their impact on protein structures and their link to disorder regions have already been spotted in the past decade. Nonetheless, the high diversity of PTM types and the multiple schemes of protein modifications (multiple PTMs, of different types, at different time, etc.) make difficult the direct confrontation of PTM annotations and protein structure data. Therefore, we analyzed the impact of the residue modifications on the protein structures at the local level. Thanks to a dedicated structure database, namely PTM-SD, a large screen of PTMs have been done and analyzed at local protein conformation levels using the structural alphabet protein blocks (PBs). We investigated the relation between PTMs and the backbone conformation of modified residues, of their local environment, and at the level of the complete protein structure. The two main PTM types (N-glycosylation and phosphorylation) have been studied in non-redundant datasets, and then four different proteins were focused, covering three types of PTMs: N-glycosylation in renin endopeptidase and liver carboxylesterase, phosphorylation in cyclin-dependent kinase 2 (CDK2), and methylation in actin. We observed that PTMs could either stabilize or destabilize the backbone structure, at a local and global scale, and that these effects depend on the PTM types.