A new perspective on Hsp104-mediated propagation and curing of the yeast prion [PSI (+) ].

Prion
Christopher W Helsen, J R Glover

Abstract

Most prions in yeast form amyloid fibrils that must be severed by the protein disaggregase Hsp104 to be propagated and transmitted efficiently to newly formed buds. Only one yeast prion, [PSI (+) ], is cured by Hsp104 overexpression. We investigated the interaction between Hsp104 and Sup35, the priongenic protein in yeast that forms the [PSI (+) ] prion.1 We found that a 20-amino acid segment within the highly-charged, unstructured middle domain of Sup35 contributes to the physical interaction between the middle domain and Hsp104. When this segment was deleted from Sup35, the efficiency of [PSI (+) ] severing was substantially reduced, resulting in larger Sup35 particles and weakening of the [PSI (+) ] phenotype. Furthermore, [PSI (+) ] in these cells was completely resistant to Hsp104 curing. The affinity of Hsp104 was considerably weaker than that of model Hsp104-binding proteins and peptides, implying that Sup35 prions are not ideal substrates for Hsp104-mediated remodeling. In light of this finding, we present a modified model of Hsp104-mediated [PSI (+) ] propagation and curing that requires only partial remodeling of Sup35 assembled into amyloid fibrils.

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Nov 15, 2011·The Journal of Biological Chemistry·Christopher W Helsen, John R Glover

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Citations

Sep 26, 2013·Nature Reviews. Molecular Cell Biology·Shannon M DoyleSue Wickner
Mar 29, 2014·European Journal of Human Genetics : EJHG·Jin ZhangXiao-Ping Dong
Jan 7, 2014·Cellular and Molecular Life Sciences : CMLS·Sean M Cascarina, Eric D Ross
Nov 27, 2015·Journal of Molecular Biology·Elizabeth A Sweeny, James Shorter
Oct 7, 2015·The Journal of Cell Biology·Jonathan O'DriscollHelen Saibil
Jun 12, 2013·The Biochemical Journal·Kuljit SinghIpsita Roy
Nov 19, 2013·FEMS Microbiology Reviews·Tatiana A ChernovaYury O Chernoff
Nov 7, 2016·Cold Spring Harbor Perspectives in Biology·Tatiana A ChernovaYury O Chernoff
Apr 11, 2018·Molecular Microbiology·Michael T AstorJustin K Hines
Aug 24, 2013·The Journal of Biological Chemistry·Stanislav A BondarevGalina A Zhouravleva
Apr 16, 2016·The Journal of Biological Chemistry·Virginia MeyerMartin Margittai
Jun 28, 2017·Current Genetics·Brian Cox, Mick Tuite
Jan 9, 2019·Frontiers in Molecular Neuroscience·Zachary T MonahanFrank P Shewmaker
Dec 6, 2019·Frontiers in Molecular Neuroscience·Lavrentii G DanilovStanislav A Bondarev

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