MOAG-4 promotes the aggregation of alpha-synuclein by competing with self-protective electrostatic interactionsYoshimura, Y., Holmberg, M. A., Kukic, P., Andersen, C. B., Mata-Cabana, A., Falsone, S. F., Vendruscolo, M., Nollen, E. A. A. & Mulder, F. A. A., 19-May-2017, In : The Journal of Biological Chemistry. 292, 20, p. 8269-8278 10 p.
Research output: Contribution to journal › Article › Academic › peer-review
Aberrant protein aggregation underlies a variety of age-related neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. Little is known, however, about the molecular mechanisms that modulate the aggregation process in the cellular environment. Recently, MOAG-4/SERF has been identified as a class of evolutionarily conserved proteins that positively regulates aggregate formation. Here, by using nuclear magnetic resonance (NMR) spectroscopy, we examine the mechanism of action of MOAG-4 by characterizing its interaction with α-synuclein (αSyn). NMR chemical shift perturbations demonstrate that a positively charged segment of MOAG-4 forms a transiently populated α-helix that interacts with the negatively charged C-terminus of αSyn. This process interferes with the intra-molecular interactions between the N- and C-terminal regions of αSyn, resulting in the protein populating less compact forms and aggregating more readily. These results provide a compelling example of the complex competition between molecular and cellular factors that protect against protein aggregation and those that promote it.
|Number of pages||10|
|Journal||The Journal of Biological Chemistry|
|Publication status||Published - 19-May-2017|
- TRIPLE-RESONANCE EXPERIMENTS, FIBRIL FORMATION, NMR EXPERIMENTS, AMYLOID FIBRILS, CHEMICAL-SHIFTS, IMPROVED SENSITIVITY, DISORDERED PROTEINS, LIGAND-BINDING, PRION PROTEIN, KINETICS