title: W8, a new Sup35 prion strain, transmits distinctive information with a conserved assembly scheme.
abstract: Prion strains are different self-propagating conformers of the same infectious protein. Three strains of the [PSI] prion, infectious forms of the yeast Sup35 protein, have been previously characterized in our laboratory. Here we report the discovery of a new [PSI] strain, named W8. We demonstrate its robust cellular propagation as well as the protein-only transmission. To reveal strain-specific sequence requirement, mutations that interfered with the propagation of W8 were identified by consecutive substitution of residues 5-55 of Sup35 by proline and insertion of glycine at alternate sites in this segment. Interestingly, propagating W8 with single mutations at residues 5-7 and around residue 43 caused the strain to transmute. In contrast to the assertion that [PSI] existed as a dynamic cloud of sub-structures, no random drift in transmission characteristics was detected in mitotically propagated W8 populations. Electron diffraction and mass-per-length measurements indicate that, similar to the 3 previously characterized strains, W8 fibers are composed of about 1 prion molecule per 4.7-Å cross-β repeat period. Thus differently folded single Sup35 molecules, not dimeric and trimeric assemblies, form the basic repeating units to build the 4 [PSI] strains.
authors.affiliation: a Molecular and Cell Biology; Taiwan International Graduate Program; Academia Sinica and National Defense Medical Center ; Taipei , Taiwan.
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Huang
authors.forename: Yuan-Chih
authors.initials: YC
authors.lastname: Chang
authors.forename: Ruben
authors.initials: R
authors.lastname: Diaz-Avalos
authors.forename: Chih-Yen
authors.initials: CY
authors.lastname: King
mesh_terms: D000483:Alleles; D017124:Conserved Sequence; D010454:Peptide Termination Factors / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: D010454:Peptide Termination Factors; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins
keywords: 5-FOA, 5-fluoroorotic acid; Aβ, amyloid β-protein; GFP, green fluorescent protein; PrP, prion protein; SC, synthetic complete; STEM, scanning transmission electron microscopy; YPD, yeast extract, peptone, dextrose; amyloid, prion strain, [PSI+], SUP35, yeast; mpl, mass per length