title: Sequence specificity and fidelity of prion transmission in yeast.
abstract: Amyloid formation is a widespread feature of various proteins. It is associated with both important diseases (including infectious mammalian prions) and biologically positive functions, and provides a basis for structural "templating" and protein-based epigenetic inheritance (for example, in the case of yeast prions). Amyloid templating is characterized by a high level of sequence specificity and conformational fidelity. Even slight variations in sequence may produce a strong barrier for prion transmission. Yeast models provide useful insight into a mechanism of amyloid specificity and fidelity. Accumulating evidence indicates that cross-species prion transmission is controlled by the identity of short sequences (specificity stretches) rather than by the overall level of sequence identity. Location of the specificity stretches determines the location and/or size of the cross-β amyloid region that controls patterns of prion variants. In some cases of cross-species prion transmission, fidelity of variant reproduction is impaired, leading to the formation of new structural variants. We propose that such a variant switch may occur due to choice of the alternatively located secondary specificity stretches, when interaction between the primary stretches is impaired due to sequence divergence.
authors: School of Biology and Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 310 Ferst Drive, Atlanta, GA 30332-0230, USA.
authors: Kathryn L
authors: KL
authors: Bruce
authors: Yury O
authors: YO
authors: Chernoff
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000378:metabolism*; D008956:Models, Chemical; D008961:Models, Structural; D011328:Prions / Q000737:chemistry* / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D012680:Sensitivity and Specificity; D016415:Sequence Alignment; D013045:Species Specificity
chemical_list: D000682:Amyloid; D011328:Prions; D029701:Saccharomyces cerevisiae Proteins