(713b) Impact of Glycosylation on Structural Properties of Intrinsically Disordered Proteins
Glycosylation is one of the most common post-translational modifications (PTMs) of proteins, which provides large proteome diversity. Previous works on glycosylation of globular proteins have revealed remarkable effects of glycosylation on protein function, altering the folding stability and structure and/or altering the protein surface, which affects the binding characteristics of proteins. Intrinsically disordered proteins (IDPs) are a broad class of proteins, which do not fold to a single three-dimensional structure under physiological conditions. They are also frequently glycosylated, yet how glycosylation affects their function remain to be elucidated: Does glycosylation affect IDP structure or binding characteristics or both? In this work, we particularly address the structural effects of glycosylation by investigating glycosylated and unglycosylated forms of two different IDPs, tau174-183 fragment and full-length human amylin (37 residues) by long replica exchange molecular dynamics simulations. Employing the current state-of-the-art all-atom models for proteins and glycans in conjunction with explicit water, we simulate these IDPs in aqueous solution for O-linked glycosylated and unglycosylated forms. By calculating the per-residue secondary structure and distance characteristics, we find that glycosylation impose only modest changes on disordered structural ensembles of IDPs for one of the protein models (Amber03*). On the other hand, with the other protein model (Charmm36) we find that glycosylation can completely destabilize a metastable beta-sheet conformation of amylin introducing a significant disorder, which might have substantial implications for functional properties and aggregation characteristics of IDPs.