NR AGLV

AU King,C.Y.

TI Supporting the structural basis of prion strains: induction and identification of [PSI] variants.

QU Journal of Molecular Biology 2001 Apr 13; 307(5): 1247-60

PT journal article

AB The [PSI] genetic element, which enhances the nonsense suppression efficiency in the yeast Saccharomyces cerevisiae, is thought to be amyloid-like aggregates of the Sup35 protein, and to self-propagate by a prion-like mechanism. Analogous to strains of the mammalian prion, variants of [PSI], with different nonsense suppression efficiencies and mitotic stabilities, can be isolated from the same yeast genetic background. In the framework of the "protein-only" hypothesis, variants of prion are assumed to be distinct conformers of the same prion polypeptide. This study aims to provide further support for the structural basis of [PSI] variation. Three variants of [PSI] were induced and distinguished by a panel of 11 single point mutations of the Sup35 protein. The variant phenotypes are intrinsically associated with [PSI] elements, presumably structurally different amyloids, rather than produced from variations in the genetic background. Differential incorporation to [PSI] variants of a Sup35 point mutation as well as N and C-terminally truncated Sup35 fragments is further demonstrated in vivo, suggesting that distinct patches of amino acid residues are involved in the assembly of [PSI] variants. These results establish a method for [PSI] variant-typing and indicate that heritable variations of amyloid structures can be derived from the same polypeptide.

MH Alleles; Fungal Proteins/chemistry/*genetics/*metabolism; Genes, Dominant/genetics; Phenotype; Point Mutation/genetics; Prions/chemistry/*genetics/*metabolism; Protein Conformation; Recombinant Fusion Proteins/chemistry/genetics/metabolism; Saccharomyces cerevisiae/chemistry/*genetics/metabolism; Support, U.S. Gov't, P.H.S.; Suppression, Genetic/*genetics; Variation (Genetics)/*genetics

AD Institute of Molecular Biophysics, Florida State University, Tallahassee, FL, 32306, USA. chihyen@sb.fsu.edu

SP englisch

PO England

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