Two-level
structure of the [PSI+] prion particles.
Dmitry S. Kryndushkin, Ilya M. Alexandrov, Vitaly V. Kushnirov, Michael D.
Ter-Avanesyan
Molecular Genetics Laboratory, Cardiology Research Center, 3rd Cherepkovskaya,
Moscow, 121552, Russia (dkrynd@cardio.ru)
Some proteins
can change their fold from normal to alternative form, called prion form, which
is able to catalyze this change. In mammals such process causes prion diseases,
however in yeast it underlies unusual mechanisms of inheritance of phenotypic
traits. The best-studied yeast prion protein is translation termination factor
eRF3, also called Sup35. The prion state of this protein may be observed by
characteristic nonsense suppressor phenotype, [PSI+], reflecting the functional
inactivation of Sup35 through its aggregation. In vitro, purified Sup35 can
form amyloid-like fibers. To obtain a new data about the structure of prion
aggregates in vivo, a novel approach for purification and analysis of prion
particles was developed. This approach allowed to show that the Sup35 prion
aggregates in vivo represent agglomerations of relatively small prion core
polymers with amyloid-like properties. In contrast to other protein complexes,
but similarly to amyloid fibers, these polymers are SDS-insoluble. The size of
polymers is characteristic of a given [PSI+] variant, and differs between the
variants. The data obtained showed that such polymers may underlie the
inheritance of [PSI+] and therefore may be referred to as elementary prion
units. The method developed may have wider application for the analysis of other
prion and amyloid phenomena both in lower and in higher eukaryotic organisms.