Hsp104 Drives ‘Protein-Only’ Positive Selection of Sup35 Prion Strains Encoding Strong [PSI+]

Details

• Alternative Title:
  Chem Biol
• Personal Author:
  DeSantis, Morgan E. ; Shorter, James
• Description:
  Structurally distinct, self-templating prion "strains" can encode distinct phenotypes and amplify at different rates depending upon the environment. Indeed, prion strain ensembles can evolve in response to environmental challenges, which makes them highly challenging drug targets. It is not understood how the proteostasis network amplifies one prion strain at the expense of another. Here, we demonstrate that Hsp104 remodels the distinct intermolecular contacts of different synthetic Sup35 prion strains in a way that selectively amplifies prions encoding strong PSI(+) and simultaneously eliminates prions encoding weak PSI(+). Hsp104 has reduced ability to fragment prions encoding weak PSI(+), but readily converts them to nontemplating forms. By contrast, Hsp104 readily fragments prions encoding strong PSI(+), but has reduced ability to eliminate their infectivity. Thus, we illuminate direct mechanisms underpinning how the proteostasis network can drive prion strain selection.
• Subjects:
  • Heat-Shock Proteins
  • Peptide Termination Factors
  • Prions
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
• Source:
  Chem Biol. 2012; 19(11):1400-1410.
• Pubmed ID:
  23177195
• Pubmed Central ID:
  PMC3508465
• Document Type:
  Journal Article
• Funding:
  1DP20D002177/DP/NCCDPHP CDC HHS/United States ; 1F31NS079009/NS/NINDS NIH HHS/United States ; 2T32GM071339/GM/NIGMS NIH HHS/United States ; DP2 OD002177/OD/NIH HHS/United States
• Volume:
  19
• Issue:
  11
• Download URL:
  https://stacks.cdc.gov/view/cdc/33480/cdc_33480_DS1.pdf
• File Type:
  [PDF - 2.42 MB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:d985bb81f5ad2b6a5aa6b19bb6344f26dedcce3de4319dbcfc09b69f2c8c2205