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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
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