Is it really the case that PRNP (https://en.wikipedia.org/wiki/PRNP) is the only known amyloid to be infectious?
One place to start other than wikipedia is this cdc site that lists know prion diseases...
After some digging, I concluded that all the diseases they listed are related to PRNP. Please, please, correct me if I'm wrong.
I'm actually going to chat with a friend in a few minutes who is a postdoc at MIT studying protein (mis)folding, and said he could help clarify. (i'll relay any new insights...)
1. The purists say prions are protein-only infectious agent; and they have a strong case since the word prion was coined as an abbreviation for "proteinaceous infectious particle". However the specific prion protein underlying these various diseases were all turning out to be the same thing.
> This evidence has led to the now widely accepted prion theory, which states that the cellular protein PrP is the sole causative agent of prion diseases; there is no nucleic acid involved. The theory holds that PrP is normally in a stable shape (pN) that does not cause disease. The protein can be flipped, however, into an abnormal shape (pD) that does cause disease. pD is infectious because it can associate with pN and convert it to pD, in an exponential process--each pD can convert more pN to pD.
What is a Prion - Scientific America
Not confused yet? Don't worry, there is a 3rd definition that has taken shape...
3. Self-templating. The word "prion" or "prion-like" has come to mean any protein that display self-templating, and is usually talked about in conjunction with epigenetic inheritance. My postdoc buddy contends this 3rd definition is winning the useage war, and so when he hears "prion", he assumes "proteins that can fold into multiple conformations with some being self-propagating." A very clear example of this usage can be found in this article on yeast (and no, it doesn't involve PRNP analogs): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319070/
PRNP is the gene encoding for "the major prion protein." Several different errors in PRNP create versions of "the major prion protein" that can be folded in a way that is bad (the prion folding). However, that is not the only way in which the proteins can fold themselves.
When lots of these proteins stuck together in an 'amyloid' (starch-like) aggregation, a misfolded (bad) shape of the protein serves as a template, folding more and more instances of the protein into the bad shape.
We consider the shape to be 'bad' because it is associated with visible symptoms of disease.
It is the prion ('bad') folding of a protein which would be infectious.
There are lots of different proteins that create amyloids, but so far all symptoms of prion-type disease for which a cause has been found have turned out to be associated with errors in PRNP.
Thanks, this is an interesting new fact to me if true. Is there a source for it?
I don't mean a source proving there are no others or something else silly like that. I mean like a review article that mentions they couldn't find any publication about any amyloid beyond PRNP-derived ones being transmitted.