Aarhus University Seal

MOAG-4 promotes the aggregation of α-synuclein by competing with self-protective electrostatic interactions

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review


  • Yuichi Yoshimura
  • ,
  • Mats Holmberg, University of Groningen, Netherlands
  • Predrag Kukic, University of Cambridge
  • ,
  • Camilla Bertel Andersen
  • ,
  • Alejandro Mata-Cabana, University of Groningen, Netherlands
  • S. Fabio Falsone, University of Graz, Austria
  • Michele Vendruscolo, University of Cambridge, United Kingdom
  • Ellen A.A. Nollen, University of Groningen, Netherlands
  • Frans Mulder

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 (α-Syn). 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 α-Syn. This process interferes with the intramolecular interactions between the N- and C-terminal regions of α-Syn, 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.

Original languageEnglish
JournalJournal of Biological Chemistry
Pages (from-to)8269-8278
Number of pages10
Publication statusPublished - 2017

    Research areas

  • Journal Article

See relations at Aarhus University Citationformats

ID: 113241786