Human proteins curing yeast prions.

Recognition that common human amyloidoses are prion diseases makes the use of the prion model systems to screen for possible anti-prion components of increasing importance. [PSI+] and [URE3] are amyloid-based prions of Sup35p and Ure2p, respectively. Yeast has at least six anti-prion systems that together cure nearly all [PSI+] and [URE3] prions arising in their absence.

Anti-Prion Systems in Turn an Avalanche of Prions into a Flurry.

Prions are infectious proteins, mostly having a self-propagating amyloid (filamentous protein polymer) structure consisting of an abnormal form of a normally soluble protein. These prions arise spontaneously in the cell without known reason, and their effects were generally considered to be fatal based on prion diseases in humans or mammals. However, the wide array of prion studies in yeast including filamentous fungi revealed that their effects can range widely, from lethal to very mild (even cryptic) or functional, depending on the nature of the prion protein and the specific prion variant (or strain) made by the same prion protein but with a different conformation.

Anti-Prion Systems Block Prion Transmission, Attenuate Prion Generation, Cure Most Prions as They Arise and Limit Prion-Induced Pathology in .

All variants of the yeast prions [PSI+] and [URE3] are detrimental to their hosts, as shown by the dramatic slowing of growth (or even lethality) of a majority, by the rare occurrence in wild isolates of even the mildest variants and by the absence of reproducible benefits of these prions. To deal with the prion problem, the host has evolved an array of anti-prion systems, acting in normal cells (without overproduction or deficiency of any component) to block prion transmission from other cells, to lower the rates of spontaneous prion generation, to cure most prions as they arise and to limit the damage caused by those variants that manage to elude these (necessarily) imperfect defenses. Here we review the properties of prion protein sequence polymorphisms Btn2, Cur1, Hsp104, Upf1,2,3, ribosome-associated chaperones, inositol polyphosphates, Sis1 and Lug1, which are responsible for these anti-prion effects.