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

ABSTRACT: While aggregation-prone proteins are known to accelerate ageing 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 C. elegans, protein aggregation and toxicity was suppressed by mutating the endogenous l

SUBMITTER: Anita Pras 

PROVIDER: S-SCDT-EMBOJ-2020-107568 | biostudies-other |

REPOSITORIES: biostudies-other