Proteins

Figure
25‐17.
Neural
degeneration
in
a
prion
infection.
This
micrograph
shows
a
slice
from


the
brain
of
a
person
who
died
of
“kuru”.
Kuru
is
a
human
prion
disease,
very
similar
to
BSE,
that


was
spread
from
one
person
to
another
by
ritual
mortuary
practices
in
New
Guinea.
The
large


Iluid‐Iilled
holes
are
places
where
neurons
have
died.
These
characteristic
holes
give
the


syndrome
the
name
of
spongiform
encephalopathy.
(Courtesy
of
Gary
Baumbach.)


©
2002
by
Bruce
Alberts,
Alexander
Johnson,
Julian
Lewis,
Martin
Raff,
Keith
Roberts,
and
Peter


Walter.


Protein
aggregates
that
cause
human
disease.



(A)
Schematic
illustration
of
the
type
of
conformational
change
in
a
protein
that
produces
material
for
a
cross‐beta


Iilament.



(B)
Diagram
illustrating
the
self‐infectious
nature
of
the
protein
aggregation
that
is
central
to
prion
diseases.
PrP
is


highly
unusual
because
the
misfolded
version
of
the
protein,
called
PrP*,
induces
the
normal
PrP
protein
it
contacts
to


change
its
conformation,
as
shown.
Most
of
the
human
diseases
caused
by
protein
aggregation
are
caused
by
the


overproduction
of
a
variant
protein
that
is
especially
prone
to
aggregation,
but
because
this
structure
is
not
infectious
in


this
way,
it
cannot
spread
from
one
animal
to
another.



(C)
Drawing
of
a
cross‐beta
Iilament,
a
common
type
of
protease‐resistant
protein
aggregate
found
in
a
variety
of
human


neurological
diseases.
Because
the
hydrogen‐bond
interactions
in
a
β
sheet
form
between
polypeptide
backbone
atoms,


a
number
of
different
abnormally
folded
proteins
can
produce
this
structure.



(D)
One
of
several
possible
models
for
the
conversion
of
PrP
to
PrP*,
showing
the
likely
change
of
two
α‐helices
into


four
β‐strands.
Although
the
structure
of
the
normal
protein
has
been
determined
accurately,
the
structure
of
the


infectious
form
is
not
yet
known
with
certainty
because
the
aggregation
has
prevented
the
use
of
standard
structural
...