Self-Perpetuating Structural States in Biology, Disease, and Genetics (2002) / Chapter Skim
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Interactions among prions and prion “strains” in yeast
Interactions among prions and prion “strains” in yeast
Pages 16-23
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From page 16... ...
Recent evidence supports the idea that prion strain variation is a result of the PrP protein's ability to propagate in different heritable prion forms (18-20~. Others, however, view the existence of prion strains as more compatible with a viral model for prion disease (21~.
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From page 17... ...
Opposite mating type yeast strains that are isogenic, sporulate efficiently when intercrossed, and contain the adel-14 allele, which permits weak and strong [PSI+] to be distinguished, were constructed by mating 74-D694 (MA Ta adel-14 trpl-289his3-~200 leu2-3,112 ura3-52)
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From page 18... ...
To determine the relative competitiveness of the tPIN+] variants, we first generated isogenic opposite mating type yeast carrying each of the tPIN+]
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From page 19... ...
variants, we crossed pairs of opposite mating type yeast harboring each of the different tPIN+] variants in all possible combinations and determined the tPIN+]
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From page 20... ...
or presumptive modifier-containing donor cytoplasm (11 of 12 independent cytoductants) was used, the data do not support the prion modifier hypothesis.
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From page 21... ...
Discussion According to the protein-only prion model, two explanations of the prion strain phenomena are possible. Prion variants may result from inherent flexibility of the tertiary structure allowing one chain of amino acids to have two or more self-perpetuating conformations that are stably inherited.
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From page 22... ...
The titration model hypothesizes that preexisting heterologous prion aggregates sequester a protein that normally inhibits prion appearance, thereby allowing other prions to appear more easily. Our current finding of no correlation between the efficiencies with which the different tPIN+]
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From page 23... ...
indicate that elucidating the molecular basis of tPIN+] strain vanation may yield impodant clues about the transmissibility of prion diseases between different species.
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