I was reading about prions and many sources say something to this effect:

"Prions may propagate by transmitting their misfolded protein state: When a prion enters a healthy organism, it induces existing, properly folded proteins to convert into the misfolded prion form. In this way, the prion acts as a template to guide the misfolding of more proteins into prion form." (Wikipedia)

How can/does a prion cause another protein to change its shape to match the prion's?

  • $\begingroup$ As the definition says, they act as a template - think "mold" $\endgroup$
    – Gerhard
    Commented Apr 26, 2016 at 21:04
  • $\begingroup$ @Gerhard Yes but how exactly does a protein mold another? Does the prion bind to it forcing it to change its shape? If so, why does that happen? If not what does happen? $\endgroup$
    – Gabriel
    Commented Apr 27, 2016 at 0:25
  • $\begingroup$ They don't misfold other proteins. They do that to other prionic protein molecules. An auto activation of sorts. $\endgroup$
    Commented Apr 27, 2016 at 3:57
  • $\begingroup$ @WYSIWYG but if prions are misfolded proteins, that would mean that when they "misfold" other "prionic protein molecules", they're misfolding other proteins...in fact "The protein that prions are made of (PrP) is found throughout the body, even in healthy people and animals...The normal form of the protein is called $PrP^C$...[which is] a normal protein found on the membranes of cells." $\endgroup$
    – Gabriel
    Commented Apr 27, 2016 at 6:18
  • 1
    $\begingroup$ @Gabriel PrPc is capable of switching but at a lower rate. This is accelerated in the presence of the alternative (beta-rich) state -- PrPsc (hence autocatalytic). I meant that the prion protein does not affect any random protein (which the statement in your question implies). The mechanism is mostly unknown. There are many other prion like proteins too, which are not pathogenic and such switches are involved in memory formation as well. $\endgroup$
    Commented Apr 27, 2016 at 8:07

2 Answers 2


It is thought that infectious prions exist as clusters forming a crystalline structure. When a protein with the same primary structure is encountered but with a different tertiary structure, the normal protein undergoes a conformational change in order to integrate into the cluster. Presumably there are molecular forces involved that induce the conformational change.



Like other forms of amyloid, aggregated prions form a beta-sheet structure, where individual beta-strands are linked together by hydrogen bonds between their extended peoptide backbones, and hydrophobic interactions between the side chains on either side of the peptide backbone. The beta-strand at each end of the beta-sheet has unpaired hydrogen bonds and hydrophobic side chains on the exposed end, which act as a template to link with an incoming prion. Thus an incoming prion molecule can be unfolded as it joins with the exposed beta-strand, rather like a zip, and a new exposed edge is formed, waiting for the next prion to join.

This chain reaction is rather like normal crystalization, except that the process of aggregation also involves a conformational change from a folded globular molecule to an extended beta strand, which is catalyzed by the presence of existing beta-strands. So the aggregation of prion effectively catalyzes more aggregation in a positive feedback loop: Once a seed has formed, the aggregation process will continue to unfold and recruit normal protein molecules. Thus BSE/CJD was originally thought to be a virus as the aggregated conformation appears to be "infectious", passing its information about its aggregated state to a native folded prion molecule.

See for example:

http://www.annualreviews.org/doi/abs/10.1146/annurev.bioeng.4.092801.094202 http://www.annualreviews.org/doi/abs/10.1146/annurev.pathmechdis.3.121806.154326 http://www.nature.com/nrn/journal/v11/n3/abs/nrn2786.html

Or just google "prion aggregation mechanism review"


You must log in to answer this question.

Not the answer you're looking for? Browse other questions tagged .