Why prions are so hard to destroy

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Nearly all organic material (like bacteria and viruses) is destroyed at temperatures above 60° Celsius. Some temperature resistant pathogens can survive slightly higher temperatures than this, but even the most hardy will be destroyed at temperatures above 150° Celsius.

But for prions these temperatures are hardly sufficient. They can survive being frozen, cooked, steamed, and even chemically treated with substances like formaldehyde and alcohol. Temperatures as high as 600° Celsius will not reliably kill them, and only in the 1000° Celsius range are they destroyed. At this temperatures, most *metals* will melt.

Why are prions so hard to destroy if they are chemically identical to the organic material inside our body already?

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Anonymous 0 Comments

The secondary structure of PrPc (the normal prion protein) is made up of three alpha helices and two beta sheets. When a prion attaches to a PrPc, a notable part of the conversion to PrPsc (the infectious prion) involves the decrease into alpha helix structures and the increase in beta sheet structures.

A high content of beta sheets in a protein makes it prone to aggregation. Beta sheets occur from the overlap of two or more linear polymers of amino acids, held by hydrogen bonds. Beta sheets are stacked on top of one another, and these strands can be parallel or antiparallel. This means that any beta sheet polymer may stack on another beta sheet, giving them a high predisposition to forming hydrogen bonds with the beta sheet structures of other proteins. It is likely this process that gives prions the ability to induce a change in conformation of adjacent PrPc proteins.

This high beta sheet content gives prions the predisposition to aggregate together and form giant structures called amyloid fibrils. Since beta sheets tend to attach to each other, the hydrophobic side chains of these amino acids will come into contact as they are trying to move inwards, away from the water. As such, the hydrophobic side chains of beta sheets will be the key in creating the hydrophobic core when stacked on to other beta sheets.

In amyloid fibrils, beta sheets of different prions are tightly stacked by various nonpolar covalent bonds, creating a strong hydrophobic core. These bonds contribute to the tightening of the beta sheet packing through the quaternary structure interactions between the elements of the amino acid side chains, which are caused by their proximity in the hydrophobic core of the amyloid structure. Among the many quaternary interactions identified, one is the formation of disulfide bridges, which have one of the highest dissociation energies among naturally occurring bonds, meaning it requires an incredibly high amount of energy to overcome these binding forces. Other such bonds work to increase the stability of amyloid fibrils by significantly lowering the energy state of this conformation (meaning it is incredibly stable). In other words, once prions form a giant polymer, it takes an incredibly high amount of energy to solubilize the fibrils. An amount of energy so high that its pretty much impossible for your body to break it down on its own and we haven’t evolved to produce enzymes that would break down the freaks of nature that are prions.

Hope this helps. I did a 4,000 word research paper on prions last year, so I’m pretty knowledgeable when it comes to prions, but I am in no way an expert.

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