Document Detail


Hsp104, Hsp70 and Hsp40 interplay regulates formation, growth and elimination of Sup35 prions.
MedLine Citation:
PMID:  18833196     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Self-templating amyloid forms of Sup35 constitute the yeast prion [PSI(+)]. How the protein-remodelling factor, Hsp104, collaborates with other chaperones to regulate [PSI(+)] inheritance remains poorly delineated. Here, we report how the Ssa and Ssb components of the Hsp70 chaperone system directly affect Sup35 prionogenesis and cooperate with Hsp104. We identify the ribosome-associated Ssb1:Zuo1:Ssz1 complex as a potent antagonist of Sup35 prionogenesis. The Hsp40 chaperones, Sis1 and Ydj1, preferentially interact with Sup35 oligomers and fibres compared with monomers, and facilitate Ssa1 and Ssb1 binding. Various Hsp70:Hsp40 pairs block prion nucleation by disassembling molten oligomers and binding mature oligomers. By binding fibres, Hsp70:Hsp40 pairs occlude prion recognition elements and inhibit seeded assembly. These inhibitory activities are partially relieved by the nucleotide exchange factor, Fes1. Low levels of Hsp104 stimulate prionogenesis and alleviate inhibition by some Hsp70:Hsp40 pairs. At high concentrations, Hsp104 eliminates Sup35 prions. This activity is reduced when Ssa1, or enhanced when Ssb1, is incorporated into nascent prions. These findings illuminate several facets of the chaperone interplay that underpins [PSI(+)] inheritance.
Authors:
James Shorter; Susan Lindquist
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-10-02
Journal Detail:
Title:  The EMBO journal     Volume:  27     ISSN:  1460-2075     ISO Abbreviation:  EMBO J.     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-10-22     Completed Date:  2008-11-17     Revised Date:  2010-09-21    
Medline Journal Info:
Nlm Unique ID:  8208664     Medline TA:  EMBO J     Country:  England    
Other Details:
Languages:  eng     Pagination:  2712-24     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Stellar-Chance Laboratories, Philadelphia, PA 19104, USA. jshorter@mail.med.upenn.edu
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphatases / chemistry
Amyloid / chemistry
Biological Transport
Gene Expression Regulation, Fungal*
Genes, Fungal
HSP40 Heat-Shock Proteins / metabolism*
HSP70 Heat-Shock Proteins / metabolism*
Heat-Shock Proteins / metabolism*
Kinetics
Models, Biological
Peptide Termination Factors
Prions / chemistry*,  metabolism,  physiology
Protein Structure, Tertiary
Saccharomyces cerevisiae / genetics,  metabolism
Saccharomyces cerevisiae Proteins / metabolism*,  physiology
Grant Support
ID/Acronym/Agency:
GM25874/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Amyloid; 0/HSP40 Heat-Shock Proteins; 0/HSP70 Heat-Shock Proteins; 0/Heat-Shock Proteins; 0/Peptide Termination Factors; 0/Prions; 0/SUP35 protein, S cerevisiae; 0/Saccharomyces cerevisiae Proteins; 143012-44-6/HsP104 protein, S cerevisiae; EC 3.6.1.-/Adenosine Triphosphatases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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