Intrinsic protein disorder and post-translational modifications

by Karin Julenius (SBC)

Wednesday 10 Feb 2010, 16:00 → 17:00 Europe/Stockholm

RB35 (RB35)

In the recent years, it has been shown that intrinsic disorder is required for the proper function and binding of proteins involved in many key biological processes. A link to post-translational modifications has also been suggested. We have gathered datasets of known positive and negative sites for six different types of post-translational modifications: N-glycosylation, mucin-type O-glycosylation, proteoglycans, C-mannosylation, phosphorylation and N-terminal acetylation. By use of state-of-the-art predictors of protein disorder, secondary structure and surface accessibility we have compared the predicted structures of positive and negative sites for each type of modification. We have also compared sequence conservation of the modified residue as given by the PSI-BLAST profile.

For several of the datasets, there is a positive correlation between modification and i) intrinsic protein disorder, ii) high surface accessibility, iii) loop/coil secondary structure, and iv) sequence conservation. From N-glycosylation, however, no clear correlations can be found to either disorder, surface accessibility or sequence conservation and loop/coil secondary structure has a small but significant negative correlation to N-glycosylation sites. We argue that these differences are due to differences at the stage when the protein is recognized by the modifying enzyme, since N-glycosylation takes place co-translationally before the protein is fully folded.