NR AUOP
AU Shkundina,I.S.; Kushnirov,V.V.; Tuite,M.F.; Ter-Avanesyan,M.D.
TI The role of the N-terminal oligopeptide repeats of the yeast Sup35 prion protein in propagation and transmission of prion variants
QU Genetics 2006 Feb; 172(2): 827-35
PT journal article
AB 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.
MH Base Sequence; Oligopeptides/*chemistry/genetics/*physiology; Phenotype; Plasmids; Prions/*chemistry/genetics/*physiology; Protein Folding; Protein Structure, Tertiary/genetics; *Repetitive Sequences, Amino Acid/genetics; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Saccharomyces cerevisiae/*chemistry/genetics/*physiology; Saccharomyces cerevisiae Proteins/*chemistry/genetics/*physiology; Sequence Deletion; *Variation (Genetics)
AD Institute of Experimental Cardiology, Cardiology Research Center, Moscow, Russia.
SP englisch
PO USA