Origins and kinetic consequences of diversity in Sup35 yeast prion fibers

2002 ◽  
Author(s):  
Angela H. DePace ◽  
Jonathan S. Weissman
Keyword(s):  
Yeast Prion

scholarly journals Compositional Determinants of Prion Formation in Yeast

2009 ◽  
Vol 30 (1) ◽  
pp. 319-332 ◽  
Author(s):  
James A. Toombs ◽  
Blake R. McCarty ◽  
Eric D. Ross
Keyword(s):  
Amino Acid ◽  
Amino Acid Composition ◽  
Amyloid Formation ◽  
Yeast Prion ◽  
Hydrophobic Residues ◽  
Predictive Methods ◽  
Infectious Proteins ◽  
Β Sheet ◽  
Eukaryotic Genomes

ABSTRACT Numerous prions (infectious proteins) have been identified in yeast that result from the conversion of soluble proteins into β-sheet-rich amyloid-like protein aggregates. Yeast prion formation is driven primarily by amino acid composition. However, yeast prion domains are generally lacking in the bulky hydrophobic residues most strongly associated with amyloid formation and are instead enriched in glutamines and asparagines. Glutamine/asparagine-rich domains are thought to be involved in both disease-related and beneficial amyloid formation. These domains are overrepresented in eukaryotic genomes, but predictive methods have not yet been developed to efficiently distinguish between prion and nonprion glutamine/asparagine-rich domains. We have developed a novel in vivo assay to quantitatively assess how composition affects prion formation. Using our results, we have defined the compositional features that promote prion formation, allowing us to accurately distinguish between glutamine/asparagine-rich domains that can form prion-like aggregates and those that cannot. Additionally, our results explain why traditional amyloid prediction algorithms fail to accurately predict amyloid formation by the glutamine/asparagine-rich yeast prion domains.

THE EVOLUTION OF THE EVOLVABILITY PROPERTIES OF THE YEAST PRION [PSI+]

Evolution ◽  
2003 ◽  
Vol 57 (7) ◽  
pp. 1498 ◽  
Author(s):  
Joanna Masel ◽  
Aviv Bergman
Keyword(s):  
Yeast Prion

scholarly journals The HAL3-PPZ1 dependent regulation of nonsense suppression efficiency in yeast and its influence on manifestation of the yeast prion-like determinant [ISP+]

2007 ◽  
Vol 12 (4) ◽  
pp. 435-445 ◽  
Author(s):  
Anna Aksenova ◽  
Iván Muñoz ◽  
Kirill Volkov ◽  
Joaquín Ariño ◽  
Ludmila Mironova
Keyword(s):  
Nonsense Suppression ◽  
Yeast Prion ◽  
Suppression Efficiency

Huntingtin Polyglutamine Fragments Are a Substrate for Hsp104 in Yeast

2021 ◽  
Author(s):  
Nicole J. Wayne ◽  
Katherine E. Dembny ◽  
Tyler Pease ◽  
Farrin Saba ◽  
Xiaohong Zhao ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Essential Role ◽  
Marked Effect ◽  
Yeast Prion ◽  
Rich Region ◽  
Polyglutamine Repeat ◽  
Prion Propagation

The aggregation of huntingtin fragments with expanded polyglutamine repeat regions (HttpolyQ) that cause Huntington’s disease depends on the presence of a prion with an amyloid conformation in yeast. As a result of this relationship, HttpolyQ aggregation indirectly depends on Hsp104 due to its essential role in prion propagation. We find that HttQ103 aggregation is directly affected by Hsp104 with and without the presence of [ RNQ + ] and [ PSI + ] prions. When we inactivate Hsp104 in the presence of prion, yeast have only one or a few large HttQ103 aggregates rather than numerous smaller aggregates. When we inactivate Hsp104 in the absence of prion, there is no significant aggregation of HttQ103; whereas with active Hsp104, HttQ103 aggregates slowly accumulate due to the severing of spontaneously nucleated aggregates by Hsp104. We do not observe either effect with HttQ103P, which has a polyproline-rich region downstream of the polyglutamine region, because HttQ103P does not spontaneously nucleate and Hsp104 does not efficiently sever the prion-nucleated HttQ103P aggregates. Therefore, the only role of Hsp104 in HttQ103P aggregation is to propagate yeast prion. In conclusion, because Hsp104 efficiently severs the HttQ103 aggregates, but not HttQ103P aggregates, it has a marked effect on the aggregation of HttQ103, but not HttQ103P.

[41] Yeast prion [Ψ+] and its determinant, sup35p

1999 ◽  
pp. 649-673 ◽  
Author(s):  
Tricia R. Serio ◽  
Anil G. Cashikar ◽  
Jahan J. Moslehi ◽  
Anthony S. Kowal ◽  
Susan L. Lindquist
Keyword(s):  
Yeast Prion

Myopathy mutations in DNAJB6 slow conformer specific substrate processing that is rescued by NEF modulation

2021 ◽  
Author(s):  
Ankan K. Bhadra ◽  
Michael J. Rau ◽  
Jil A. Daw ◽  
James A.J. Fitzpatrick ◽  
Conrad C. Weihl ◽  
...  
Keyword(s):  
Chaperone Activity ◽  
Specific Substrate ◽  
Yeast Prion ◽  
Protein Aggregate ◽  
Client Proteins ◽  
Chaperone Interactions ◽  
Chaperone Network ◽  
Shock Proteins ◽  
Substrate Processing

Molecular chaperones, or heat shock proteins (HSPs), protect against the toxic misfolding and aggregation of proteins. As such, mutations or deficiencies within the chaperone network can lead to disease. In fact, dominant mutations in DNAJB6 (Hsp40/Sis1), an Hsp70 co-chaperone, leads to a protein aggregate myopathy termed Limb-Girdle Muscular Dystrophy Type D1 (LGMDD1). DNAJB6 client proteins and co-chaperone interactions in skeletal muscle are not known. Here, we used the yeast prion model client in conjunction with in vitro chaperone activity assays to gain mechanistic insights, and found that LGMDD1 mutants affect Hsp40 functions. Strikingly, the mutants changed the structure of client protein aggregates, as determined by altered distribution of prion strains. They also impair the Hsp70 ATPase cycle, dimerization, and substrate processing and consequently poison the function of wild-type protein. These results define the mechanisms by which LGMDD1 mutations alter chaperone activity and provide avenues for therapeutic intervention.

Observation of Amyloid-Like Fibers of the Sup35 Protein from Saccharomyces Cerevisiae

2000 ◽  
Vol 6 (S2) ◽  
pp. 664-665
Author(s):  
Anthony S. Kowal ◽  
Thomas Scheibel ◽  
Susan L. Lindquist
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Protein Conformation ◽  
Prion Proteins ◽  
Translation Termination ◽  
Polarized Light ◽  
Yeast Cells ◽  
Yeast Prion ◽  
Epigenetic Modifier ◽  
Insoluble Form

In the yeast Saccharomyces cerevisiae, [PST] acts as an epigenetic modifier of translation termination efficiency. [PSI+] can be passed through generations of yeast cells via changes in protein conformation rather than changes in DNA or RNA, and has thus been referred to as a yeast prion. The [PSI+] determinant is the Sup35 protein. Sup35 can exist in two states - soluble and insoluble. Soluble Sup35 functions in translation termination, but when insoluble, stop codons are read through, resulting in incorrect protein products.Sup35 is composed of three distinct domains, N, M, and C. The N region is rich in glutamine and asparagine and is required for the [PST] phenotype to exist. M is a highly charged domain, and no specific function has been assigned to it. C is essential in yeast, as it is responsible for translation termination. The insoluble form of Sup35 has characteristics reminiscent of other prion proteins - in vitro it binds to the dye Congo Red and it exhibits apple green birefringence in polarized light.

scholarly journals Hsp40 Interacts Directly with the Native State of the Yeast Prion Protein Ure2 and Inhibits Formation of Amyloid-like Fibrils

2007 ◽  
Vol 282 (16) ◽  
pp. 11931-11940 ◽  
Author(s):  
Hui-Yong Lian ◽  
Hong Zhang ◽  
Zai-Rong Zhang ◽  
Harriët M. Loovers ◽  
Gary W. Jones ◽  
...  
Keyword(s):  
Prion Protein ◽  
Yeast Prion ◽  
Native State
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