Defining key residues of the Swi1 prion domain in prion formation and maintenance

Dustin K. Goncharoff, Raudel Cabral, Sarah V. Applebey, Manasa Pagadala, Zhiqiang Du*, Liming Li

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Prions are self-perpetuating, alternative protein conformations associated with neurological diseases and normal cellular functions. Saccharomyces cerevisiae contains many endogenous prions, providing a powerful system to study prionization. Previously, we demonstrated that Swi1, a component of the SWI/SNF chromatin-remodeling complex, can form the prion [SWI1]. A small region, Swi11–38, with a unique amino acid composition of low complexity, acts as a prion domain and supports [SWI1] propagation. Here, we further examine Swi1138 through site-directed mutagenesis. We found that mutations of the two phenylalanine residues or the threonine tract inhibit Swi1138 aggregation. In addition, mutating both phenylalanines can abolish de novo prion formation by Swi11–38, whereas mutating only one phenylalanine does not. Replacement of half of or the entire eight-threonine tract with alanines has the same effect, possibly disrupting a core region of Swi1138 aggregates. We also show that Swi1138 and its prion-fold-maintaining mutants form high-molecular-weight, SDS-resistant aggregates, whereas the double-phenylalanine mutants eliminate these protein species. These results indicate the necessity of the large hydrophobic residues and threonine tract in Swi1138 in prionogenesis, possibly acting as important aggregable regions. Our findings thus highlight the importance of specific amino acid residues in the Swi1 prion domain in prion formation and maintenance.

Original languageEnglish (US)
Article numbere00044-21
JournalMolecular and cellular biology
Volume41
Issue number7
DOIs
StatePublished - Jun 2021

Keywords

  • Prion domain
  • Prionogenesis
  • Protein aggregation
  • SWI
  • SWI/SNF
  • Saccharomyces cerevisiae
  • Swi1
  • Yeast

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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