Washington University in St. Louis

3rd Publication for Kate Keefer in the True Lab

Congratulations to Kate Keefer!  This is Kate's 3rd publication from her predoctoral work in Dr. Heather True's lab.  


Kathryn M. Keefer, Kevin C. Stein and Heather L. True  (2017)  Heterologous prion-forming proteins intereact to cross-seed aggregation in Saccharomyces cerevisiae.  Scientific Reports [E-published July 19]

Abstract:  The early stages of protein misfolding remain incompletely understood, as most mammalian proteinopathies are only detected after irreversible protein aggregates have formed. Cross-seeding,where one aggregated protein templates the misfolding of a heterologous protein, is one mechanism proposed to stimulate protein aggregation and facilitate disease pathogenesis. Here, we demonstrate the existence of cross-seeding as a crucial step in the formation of the yeast prion [PSI +], formed by the translation termination factor Sup35. We provide evidence for the genetic and physical interaction of the prion protein Rnq1 with Sup35 as a predominant mechanism leading to self-propagating Sup35 aggregation. We identify interacting sites within Rnq1 and Sup35 and determine the effects of breaking and restoring a crucial interaction. Altogether, our results demonstrate that single-residue disruption can drastically reduce the effects of cross-seeding, a finding that has important implications for human protein misfolding disorders.

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