In this seminar, I will tell you how the
presence of one yeast prion can enhance
the appearance of other yeast prions.
According to the prion
paradigm in yeast cells can
propagate prion proteins in either
the normal form or the prion form.
When propagated in the prion form,
they have a different phenotype than in
cultures where the protein is
propagated and the normal form.
Cells with the prion in the normal
form can be converted into
prion cultures by being
infected with prion seed.
Evidence suggests that
the prion seed is a fiber and
that the normal molecules
join this fiber at the ends.
The growth of the prion fiber is limited
by the fact that it only has two ends.
And as you could imagine, its ability to
segregate into budding daughter cells is
also limited by the number of prion
seeds that are present in the mother.
The Hsp104 chaperone whose
activity is known to disaggregate
aggregated proteins provides
the important activity for
the prion of cutting these fibers into
pieces, which provides additional ends and
additional seeds that can then
segregate into the daughters.
In the absence of Hsp104 of course,
the prions are not cut and they fail
to segregate and are lost, leading
to the curing of cells of the prion.
This also explains how the low
levels of guanidine hydrochloride,
known for many years to cure cells
of prions works and it does so
we now know by inhibiting
the activity of the Hsp104 chaperone.