Repository logo

The cellular modifier MOAG-4/SERF drives amyloid formation through charge complementation.

Published version



Change log



While aggregation-prone proteins are known to accelerate aging and cause age-related diseases, the cellular mechanisms that drive their cytotoxicity remain unresolved. The orthologous proteins MOAG-4, SERF1A, and SERF2 have recently been identified as cellular modifiers of such proteotoxicity. Using a peptide array screening approach on human amyloidogenic proteins, we found that SERF2 interacted with protein segments enriched in negatively charged and hydrophobic, aromatic amino acids. The absence of such segments, or the neutralization of the positive charge in SERF2, prevented these interactions and abolished the amyloid-promoting activity of SERF2. In protein aggregation models in the nematode worm Caenorhabditis elegans, protein aggregation and toxicity were suppressed by mutating the endogenous locus of MOAG-4 to neutralize charge. Our data indicate that MOAG-4 and SERF2 drive protein aggregation and toxicity by interactions with negatively charged segments in aggregation-prone proteins. Such charge interactions might accelerate primary nucleation of amyloid by initiating structural changes and by decreasing colloidal stability. Our study points at charge interactions between cellular modifiers and amyloidogenic proteins as potential targets for interventions to reduce age-related protein toxicity.



MOAG-4, SERF, amyloid, protein aggregation, protein quality control, Amino Acid Sequence, Amyloid, Amyloidogenic Proteins, Animals, Binding Sites, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Gene Expression Regulation, HEK293 Cells, Humans, Hydrophobic and Hydrophilic Interactions, Intracellular Signaling Peptides and Proteins, Nerve Tissue Proteins, Peptides, Protein Aggregates, Protein Array Analysis, Protein Binding, Signal Transduction, Static Electricity, alpha-Synuclein

Journal Title


Conference Name

Journal ISSN


Volume Title


Springer Science and Business Media LLC