The structure of PrPC (left
of above figure) is primarily alpha-helix (tubular
features) with limited beta-structures (waved
arrows) connected by loop features (linear
sections)
and attached to cell membranes by a GPI anchor (yellow
end).
Either by mutation of the protein's amino
acid sequence (Familial TSEs)
or by interaction with infectious
PrPSc, the protein adopts more of a beta-structure; PrPSc
(right of above figure). In many TSEs this is the predominant from of PrP found
in brain (i.e., not all of the PrPSc is converted to PrPSc
27-30). In addition, proteins similar in size to PrPSc 27-30 are
found in normal brain (i.e. PrPC 27-30 although they are not resistant
to exogenous proteinase K).
In conditions where amyloid plaques form,
a cleaved (
) protease-resistant
core PrPSc
27-30 is present in the extracellular regions (left of figure). This truncated
protein (
) may
have loss most if not all of its alpha-helical structure after the cleavage
(removal) of 50-80 amino acids from the beginning (N-terminus) of the protein
and the last 70-80 amino acids from the end (C-terminus) of the
protein. Multiple beta-structures (waved
arrows) lying within a plane probably
form a beta-sheet (further llustrated as either as lying on a flat surface with
a dangling loop region (
)
or as a Greek key motif (
)
with an additional
beta-structure made from the loop region).
The resulting 27-30 aggregates in certain
forms of TSE forming amyloid plaques. The structure of the plaques is not known
but probably results from stacking of multiple
beta-sheets (right of figure showing 9 proteins alternating colors for illustration
between orange
and green).
At this point, the original PrPC
has been mis-folded to form PrPSc, cleaved to PrPSc 27-30,
released into the extracellular environment and finally in some cases stacked
within plaques.
PrPSc (but probably not PrPSc
27-30) may be held together by intramolecular cystine bonds (normally the protein
has a single intermolecular bond).
click on image for more information about cystine bonds and stabilizing abnormal
prion structures
click
on image for more on PrP fragment analysis and use in strain typing