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not classical amyloids. Indeed, Fourier-transform infrared spec-
troscopy (FTIR) reveals a large proportion of
-helical structure
within the fibrils, very limited structural change upon assembly of
soluble Ure2p into fibrils, and the absence of increased absorbance
in the amyloid specific band (1618-1623 cm
α
−1
42
Further, X-ray fibre
diffraction patterns generated from partially aligned Ure2p fibrils
are inconsistent with a cross-
).
structure and compatible instead
with the regular packing of globular Ure2p molecules.
β
64
Finally, the
findings that (i) fibrils made of full-length Ure2p exhibit a punctate
appearance on averaged high-resolution cryoelectron micrographs
only compatible with a highly repetitive structure made up of
ordered arrangement of globular Ure2p molecules stacked in a helical
array
65
and (ii) Ure2p molecules are not involved in a systematically
H-bonded
-sheet structure within the fibrils as determined using
hydrogen/deuterium exchange studies and mass spectrometry,
β
66
strongly suggest that Ure2p fibrils are not conventional amyloids.
Fibrils made following dilution from denaturant of unfolded
HET-s are of amyloid nature based on their FTIR absorbance
spectrum.
It is, however, not clear yet whether authentic HET-s
forms such fibrils.
46
6.5
Structural Basis of Yeast Prion Propagation
It is widely believed that prions propagate through unfolding or
misfolding events. Two mechanistic models have been proposed to
illustrate how following this seminal folding event prions propagate:
the
template
assistance
1,67,68
and
the
seeded-polymerization
69
The infectious misfolded form interacts physically with the
native soluble form and transforms the latter into a misfolded form
following the template-assistance model (Fig. 6.4a). As the infectious
homodimer/polymer is capable of dissociating/breaking, the
conversion process of the native pool of prion into misfolded forms
is exponential. In the template-assistance model, the infectious
form acts somehow as a template facilitating the occurrence of an
energetically unfavourable protein-folding event. A variant of this
scenario has been proposed where the interaction between an
unidentified enzyme or chaperone and native prion proteins could
favour the protein folding event at the origin of the prion form.
models.
70
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