The most comprehensive theory so far put forward as to the identity
of the infective agent of TSEs
is that it comprises solely of a mutated form of the PrP
protein made naturally by the body. It has been shown that the
protein exists in two different forms, one found in the bodies
of most animals and one found only in animals that are developing
or have developed a TSE. It is proposed
by the scientist Keh-Ming Pan that the natural protein form includes
sections where the protein backbone is twisted in a specific type
of spiral, the Alpha helices. But when affected by the disease
these sections become fully extended, forming Beta strands, which
collect together to form a Beta sheet structure, giving the molecule
much greater stability and making it much more resistant to being
broken down.
Studies by other scientists on the properties of PrPc
and PrPsc, as they were called, discovered
that the central structure of the PrPc
is in fact 4 helices joined closely together, with a number of
amino acids joined to the molecule about them. It is thought that
a change to one of these amino acids during mutation destabilises
the Alpha helices structure, making the protein more likely to
flip to the Beta sheet configuration (the flipping of the protein
can also occur randomly, without outside stimulus, giving rise
to sporadic cases of TSE diseases).
Other research by Jack Nguyen, Byron Caughey and Peter Lansbury
has shown that the mutated PrPsc can
cause mutation of otherwise healthy PrPc
proteins simultaneously when they come into contact. This gives
the PrPsc the ability to multiply
which it needs to be an infective agent.
