Shkundina, I.S. and Kushnirov, V.V. and Tuite, M.F. and Ter-Avanesyan, M.D. (2006) The role of the N-terminal oligopeptide repeats of the yeast Sup35 prion protein in propagation and transmission of prion variants. Genetics, 172 (2). pp. 827-835. ISSN 0016-6731.
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The cytoplasmic [PSI+] determinant of Saccharomyces cerevisiae is the prion form of the Sup35 protein. Oligopeptide repeats within the Sup35 N-terminal domain (PrD) presumably are required for the stable [PSI+] inheritance that in turn involves fragmentation of Sup35 polymers by the chaperone Hsp104. The nonsense suppressor [PSI+] phenotype can vary in efficiency probably due to different inheritable Sup35 polymer structures. Here we study the ability of Sup35 mutants with various deletions of the oligopeptide repeats to support [PSI+] propagation. We define the minimal region of the Sup35-PrD necessary to support [PSI+] as amino acids 1-64, which include the first two repeats, although a longer fragment, 1-83, is required to maintain weak [PSI+] variants. Replacement of wild-type Sup35 with deletion mutants decreases the strength of the [PSI+] phenotype. However, with one exception, reintroducing the wild-type Sup35 restores the original phenotype. Thus, the specific prion fold defining the [PSI+] variant can be preserved by the mutant Sup35 protein despite the change of phenotype. Coexpression of wild-type and mutant Sup35 containing three, two, one, or no oligopeptide repeats causes variant-specific [PSI+] elimination. These data suggest that [PSI+] variability is primarily defined by differential folding of the Sup35-PrD oligopeptide-repeat region.
|Additional information:||0016-6731 (Print) Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.|
|Uncontrolled keywords:||Base Sequence Oligopeptides/*chemistry/genetics/*physiology Phenotype Plasmids Prions/*chemistry/genetics/*physiology Protein Folding Protein Structure, Tertiary/genetics *Repetitive Sequences, Amino Acid/genetics Saccharomyces cerevisiae/*chemistry/genetics/*physiology Saccharomyces cerevisiae Proteins/*chemistry/genetics/*physiology Sequence Deletion *Variation (Genetics)|
|Subjects:||Q Science > QR Microbiology|
|Divisions:||Faculties > Science Technology and Medical Studies > School of Biosciences > Protein Science Group|
|Depositing User:||Mick Tuite|
|Date Deposited:||02 Sep 2008 14:41|
|Last Modified:||14 Jan 2010 14:20|
|Resource URI:||http://kar.kent.ac.uk/id/eprint/5448 (The current URI for this page, for reference purposes)|
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