Regulation and aggregation of intrinsically disordered peptides
Abstract
The microtubule-regulating protein tau is a prototypical intrinsically disordered protein (IDP) that plays an important physiological role in the human body; however, aggregates of tau are a pathological hallmark of Alzheimer's disease. Here we demonstrate through simulations and experiments with an aggregating tau fragment that cosolvent interactions can significantly affect the balance between hydrogen bonds and salt bridge formation in IDPs, subsequently determining their preferred conformations. These subtle perturbations can dramatically shift IDPs from compact ensembles to extended ones, thereby influencing aggregate formation. These results lend considerable insight into the biophysics of the regulation and aggregation of IDPs.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- March 2015
- DOI:
- 10.1073/pnas.1418155112
- Bibcode:
- 2015PNAS..112.2758L