Normal and pathogenic prions

[Dov]

Re

Scientific American July 2004

Detecting Mad Cow Disease,

Stanley B. Prusiner

 

 

Genesis and replication modes of pathogenic prions curiously connote

initial genesis and evolution of life, maybe from an RNA-related

conformation. In both cases the process-enabling-moving

circumstances are presence of the precursors of the Bingo

Conformation plus a favorable energy balance.

 

Is it probable/possible, therefore, that the switch from normal to

pathogenic prions is enabled and moved by a replacement of a

component amino-acid such as tryptophane/niacin ?

 

Dov Henis

[admiral_ju00]

That's possible. After all, prions are simply proteins that are misfolded.

[Dov]

Yes, the pathogenic prions are "misfolded" plus replicating plus resist enzymatic digestion, but what is most interesting: is there any chemical change involved in the transition of normal to pathogenic prions, that leads to the changed characteristics of

normal-to-pathogenic prions ?

[LucidDreamer]

Yes there are. There actually seem to be several methods. One of them is them is a gene sequence mutation that results in an incorrect amino acid sequence. Here is a link to a very informative journal article with many links to other good articles.

http://www.pnas.org/cgi/content/full/95/23/13363#B16

[Dov]

Thank you for suggesting the link. However, at my advanced age (1) I may not live long enough to read the whole article properly, (2) I try reading most recently updated information, and (3) I feel uneasy at the apparently contrasting statements in the abstract:

 

(a)"cellular PrP (PrPC) is converted into PrPSc through a posttranslational process"

 

(b)"The species of a particular prion is encoded by the sequence of the chromosomal PrP gene of the mammals in which it last replicated"

 

I raise the subject because back in the early '50s I effected encephalomyelitis in fowls by inadequate levels of niacin or tryptophane and found that the minimal required level of these amino acids for the type of fowl was related to the physiology/activity characteristics of the different fowl types.

 

My gut feeling ( obviously not experimental evidence ) is that PrPc to PrPSc conversion is indeed a "posttranslational conversion", initiated and maintained by a replacement of an amino acid, initiated and chain-reacting due to an energetically effected equation situation, on one side the combined suspended/soluble presence of PrPc and its precursors and on the other side the precipitating PrPSc.

[Dov]

Just read (The Scientist) updated reports that purified PrPSc do not replicate and that indeed various PrPSc's differ in amino acid component(s) .

 

Therefore it is required now to learn if tagged PrPc shows up in the PrPSc, or not, for finding if the PrPSc is formed from PrPc, or if it is formed instead of and to the exclusion of PrPc.

 

Also these data enhance the probability that the PrPSc's includes an adjunct "agent" , lost upon PrPSc purification, that directs the preferred formation of PrPSc.