Hi
JohnM,
I was a bit hazy
on what 'prion' exactly referred to myself. Here's what I've dug
up.
Prion - short
for "proteinaceous infectious particle", specifically ones that lacks
nucleic acid (see quote below). The term was coined by Stanley Prusiner at
Univ. of Cal. Med School in 1982. Prions are proteins and contain no RNA
or DNA. he won a Nobel Price for his work on prions in 1997.
PrP - short for "prion protein".
From what I
read, neither "prion" nor "PrP" automatically imply that they
refer only to the "misfolded" version of
the proteins. However, many websites talk about prions as
if the term 'prion' did refer only to the "misfolded" versions. Those
sites appear to me to be incorrect.
Prusiner's Nobel
lecture (in PDF form):
Prusiner's paper in "Science" (1997, No. 5336, Oct.,
p. 245-251) is available free at:
In the Science
paper, footnote 1 is as follows:
Prions are defined as proteinaceous
infectious particles that lack nucleic acid. PrPC is the cellular
prion protein; PrPSc is the pathologic isoform. Amino-terminal
truncation during limited proteolysis of PrPSc produces PrP 27-30
(so named because this protease-resistant core of PrPSc migrates
at ~27 to 30 kD).
Further on in
the paper:
PrPSc is the major, and very
probably the only, component of the infectious prion particle.
PrPSc formation is a posttranslational process involving only a
conformational change in PrPC
So,
when talking about a prion-caused disease, we should
probably not say that "the prion causes x", but rather something
like: "PrPSc causes x" or "the pathological isoform of PrP causes x".
Otherwise, we would be saying something analogous to "genes cause x" when we
really mean that "mutated genes cause x".
I am uncertain
if all currently identified pathological isoforms of prions are termed
"PrPSc", or if there are other terms (for pathological isoforms of PrP found
in some other species, for example), but I believe it does refer to all forms,
even though the "Sc" in "PrPSc" apparently initially was a reference to
scrapie (the sheep version of BSE). From the Nobel
lecture:
"The amino acid sequence of PrPSc
corresponds to that encoded by the PrP gene of the mammalian host in which
it last replicated. In constrast to pathogens with a nucleinc-acid genome
that encodes strain-specific properties in genes, prions encipher these
properties in the tertiary structure of PrPSc." (p.
4)
When is a
protein a prion?
The answer to
this is still a bit unclear to me. I speculate from what I read that a
protein can be a called a prion based not necessarily on specific amino acid
sequence (which varies with species), but on some (mostly) functional
criteria:
1) if a protein
is coded for in the genome of the species under study
2) and if it can
be folded into the two isoforms representing PrPC and
PrPSc
3) and if the
PrPC isoform is normally occurring and functional in the species under
study
4) and if the PrPSc isoform is not functional in that
species
5) and if the
PrPSc isoform can convert the PrPC in the organism into
PrPSc
6) and if the
PrPSc isoform is highly resistant to destruction by
proteasomes.
Other "what is a
prion?" sites:
Regards,
Tim
Tim and All,
I told several times that I am a
virgin-minded layman (=stupid) in the biology-related sciences up from the
macromolecules. Question:
in superficial reading I got the impression
that "PRION" is used as the specific villain in mad cow disease. I thought
it is a 'small' piece of proteinatious molecule with an inorderly folding.
Maybe the latter is pertinent to MCD only and prions can be 'orderly folded
protein
midgets' with RNA only, as well? Many other
animals (fish, etc.) have prions, do they spread mad fish disease? I don't
think so.
I find it unreasonable to 'wait 30 months'
or any, since infected remnants (mentioned are: placentas) of MCD cows
stay for years in pastures ready to infect deer, hare etc, which then
do the favor for the coyotes, wolves, people and other predators. That is
pertinent to PA, NJ, NY, MN, and all other states as well, not only the
West.
Agribiz - as any other successful biz does
not care beyond making money today. That's why that stupid law was concocted
in the US.
Suicidal behavior? for the others. Not for
"me". The government owning oligarchy will feed safely on their private
(organic) sources of their food staple, even if millions fall over like mad
cows.
Protein folding is big deal. I made
experiments myself (El Micr.-ly controlled) "straightening out" protein (and
the like) molecules, froze them in unfolded state, then restored the
mobility and it reformed the orig. folding perfectly, no matter in what
'changed' environment. So a "misfolding" is more than an esthetic nuisance.
It forms the joining sites (or hides them)
for enzymes, etc., so the conformation is a fundamental adage to the "life
processes".
I asked the question in the 1st par because
it seems that we have mixed info and I don't have the time to study along
books on the proteinatious materials of recent. The old ones I know do not
include the word prion. Just as the recent ones do not include words which
will be coined in the future, when we (hopefully) will learn more about
nature. We can use more knowledge.
I hope the US science will come up with a
better SAFE solution than cremating 45million cows (and bulls!). It's a mad
mad world.
John M