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Prions are a crazy, crazy phenomenon. From wikipedia: > A protein as a standalone infectious agent stands in contrast to all other known infectious agents such
by shmageggy 11y ago
Prions are a crazy, crazy phenomenon. From wikipedia:
> A protein as a standalone infectious agent stands in contrast to all other known infectious agents such as viruses, bacteria, fungi, and parasites, all of which contain nucleic acids (DNA, RNA, or both)
In my layman's understanding, they're like this bizarre edge case in the way proteins interact. Of all the myriad way a protien can fold, it happens to find one that induces the same malformation when it interacts with another protein. To me, it almost seems like as much of a mathematical/geometrical problem as a biological one. In any case, very interesting from the perspective of emergent behavior in complex systems.
- danieltillett 11y agoPrions are one of those great examples that in biology every rule has an exception.
- hga 11y agoThe rule I like here is that things like viruses and prions exist because they can.
- pklausler 11y agoWhich may well be the only reason we exist, too.
- ethbro 11y agohttp://www.radiolab.org/story/cellmates/ http://www.radiolab.org/story/cellmates/ The most recent Radiolab was about an idea that the existence of cellular organelles are the product of an extremely unlikely merging of two cells that didn't immediately die afterwards. Stemming from the observation that we had an extremely long period of simple life, coupled with a sudden explosion where life rapidly increased in size and complexity. A 0.0...01% likelihood event will still happen, given an entire planet of simple cells and hundreds of millions of years.
- Joof 11y agoIt makes sense that we find this on occasion (once you accept that there exists some combination of folding that produces this). Once one protein folds in a way that can induce the same modification, it will replicate rather quickly. Are there proteins that cause looping multiple-step reactions as well? Maybe that's what this is and I need to read more :p.
- gilleain 11y agoWhat do you mean by "looping multiple-step reaction"? If prions are "A'(A)->A'", do you mean "A'(B)->B', B'(A)->A'"? (Where A/A' are different forms of the same structure and A(B)->C means A acts on B to make C).
- Joof 11y agoYeah. Probably wouldn't work / there would be some weird equilibrium.
- gilleain 11y agoWell, I don't know of any protein folding examples, but it seems a lot like an "autocatalytic cycle" which is an interesting part of origin-of-life theories. Stuart Kauffman wrote some things about this, but here is a counterpoint from Leslie E Orgel: http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.0060018 http://journals.plos.org/plosbiology/article?id=10.1371/jour...
- Joof 11y agoMakes logical sense that it would be a part of life (once you can synthesize a few things from a given one thing you can build all sorts of logical structures...), but I see there are tons of biological probabilities at play that I don't understand. How did school manage to make biology so boring? They did it with math too, so I shouldn't be surprised, but damn. Would love resources on an intro to bio for the CS folk. I'm sure there are some good ones out there.
- 11y ago
- omegaham 11y agoYep. It makes me think of programming quines. Except deadly.
- gilleain 11y agoYou can break it down further into two separate surprises: 1) The normal form (PrPc) is mostly helical, while the diseased form (PrPsc) is mostly beta-sheet. 2) PrPsc catalyses the switch from helix to sheet. I find the first to be more surprising. After all, chaperones (https://en.wikipedia.org/wiki/Chaperone_(protein) https://en.wikipedia.org/wiki/Chaperone_(protein)) exist to catalyse folding of proteins - although that is from partly folded to fully folded.
- Brakenshire 11y agoIt's the same principle as the nucleation process which turns clouds into rain.
- acjohnson55 11y agoWhat's also wild to me is that, conversely, RNA can have enzyme-like behavior [1], including catalyzing their own synthesis [2]. Both types of molecules are amazingly versatile. [1] https://en.wikipedia.org/wiki/Ribozyme https://en.wikipedia.org/wiki/Ribozyme [2] https://en.wikipedia.org/wiki/Autocatalysis https://en.wikipedia.org/wiki/Autocatalysis
- minikomi 11y agoThere's lots of weird stuff on the edge of "life" https://en.wikipedia.org/wiki/Viroid https://en.wikipedia.org/wiki/Viroid
- lawpoop 11y agoThere's also a hypothesis, to which I am partial, that RNA was the original self-replicating molecule[1], from which all life evolved, and that DNA was a later development. DNA gets transcripted into RNA before it codes proteins, so an original RNA moelcule, being both a catalyst and a data store, eventually developed variations that in turn also produced pure catalysts (proteins) and a pure data store (DNA). But it's still the lynchpin of the reproduction process. [1] https://en.wikipedia.org/wiki/RNA_world https://en.wikipedia.org/wiki/RNA_world
- CharlesW 11y agoIs it reasonable to think of it like this: RNA is procedural, and DNA is declarative? RNA : PostScript :: DNA : PDF?
- po 11y agoI was thinking that Prions remind me of biological Ice-nine and sure enough there's a mention of it in the wikipedia article for Ice-nine: Ice-nine has been used as a model to explain the infective mechanism of mis-folded proteins called prions which are thought to catalyze the mis-folding of the corresponding normal protein leading to a variety of spongiform encephalopathies such as kuru, scrapie and Creutzfeldt–Jakob disease. https://en.wikipedia.org/wiki/Ice-nine https://en.wikipedia.org/wiki/Ice-nine
- FoeNyx 11y agoPrions remind me of the apocalyptic theory about strangelets and strange matter : "One speculation that has resulted from the idea is that a strangelet coming into contact with a lump of ordinary matter could convert the ordinary matter to strange matter." https://en.wikipedia.org/wiki/Strangelet#Dangers https://en.wikipedia.org/wiki/Strangelet#Dangers Also mere ideas could also been seen as some mind-folding catalysts, language being the infective mechanism. Variants of this trope often appear in literature (science-fiction or not). For example in "Viruses of the Mind" : "Richard Dawkins analyzes the propagation of religious ideas and behaviors as a memetic virus" https://en.wikipedia.org/wiki/Viruses_of_the_Mind https://en.wikipedia.org/wiki/Viruses_of_the_Mind
- ryandvm 11y agoThe most terrifying thing about prions is that since they're not reliant on the usual processes for reproduction, they're not susceptible to our usual weapons for dealing with disease (e.g. cooking, antibiotics/antiseptics, vaccines).
- Dutchie 11y agoDon't these type of complex molecules get completely destroyed when cooked? (Total layman here, so no rhetorical question).
- jahnu 11y agohttp://www.today.com/id/5479931/ns/today-today_health/t/how-deadly-prions-are-destroyed/ http://www.today.com/id/5479931/ns/today-today_health/t/how-... "Incineration is possible, but it isn't as easy as burning the carcass in a fire. Temperatures of more than 1,100 degrees Fahrenheit — sometimes up to 1,800 degrees — are required to effectively neutralize prions. Unlike most bacteria, regular cooking won't help at all. "Disposal issues are tough," says Barbara Powers, director of Colorado State University's Veterinary Diagnostic Laboratory."
- kijin 11y agoProteins aren't destroyed by cooking. Otherwise you would not be able to get any proteins from cooked meat or beans. The only reliable method that I'm aware of to denature proteins without making the whole thing inedible is hydrolysis. Gelatin is made from collagen in the skin, bones, and connective tissues of various animals, but Jell-O is generally considered safe.
- kordless 11y ago> induces the same malformation when it interacts with another protein Sounds like a kill switch to me.
- rdtsc 11y agoSo it is a bit like a self-replicating cellular automaton. Like game of life examples, except, well... in real life.
- nonbel 11y ago>"Of all the myriad way a protien can fold, it happens to find one that induces the same malformation when it interacts with another protein." It doesn't really "just happen", amyloids consist of peptides folded into beta-sheets and aggregates of these seem to be the most thermodynamically stable structures it is possible for polypeptide chains (regardless of sequence) to form: "From a wide range of in vitro experiments on peptides and proteins we now know that the formation of amyloid structures is not a rare phenomenon associated with a small number of diseases but rather that it reflects a well-defined structural form of the protein that is an alternative to the native state — a form that may in principle be adopted by many, if not all, polypeptide sequences [...] These observations, therefore, have led to the remarkable conclusion that, at the concentrations present in living systems, the native states may not always represent the absolute free energy minima of the corresponding polypeptide chains — the native form of a protein could in some cases simply be a metastable monomeric (or functionally oligomeric) state that is separated from its polymeric amyloid form by high kinetic barriers" http://www.ncbi.nlm.nih.gov/pubmed/24854788 http://www.ncbi.nlm.nih.gov/pubmed/24854788 Edit: I realized some people might not be aware of the connection to prions. Here it is from the same wikipedia page as cited by the parent: "All known prions induce the formation of an amyloid fold, in which the protein polymerises into an aggregate consisting of tightly packed beta sheets." https://en.wikipedia.org/wiki/Prion https://en.wikipedia.org/wiki/Prion
- shmageggy 11y agoIf that's the case, why don't we see them more often?
- nonbel 11y agoFrom the same paper: "Many of the characteristics of proteins that enable the avoidance of aggregation, and amyloid formation in particular, are encoded by their amino acid sequences116. The elucidation of this code has enabled the identification of factors that determine the intrinsic aggregation propensity of these molecules117, 118, 119. Hence, it has been realized that globular proteins fold into structures that sequester aggregation-prone regions in their interior; in addition, typical features of the folding process, such as very high cooperativity, generate considerable kinetic barriers to the conversion of folded proteins into aggregation-prone species50, 120. Furthermore, specific patterns of residues, such as alternating hydrophobic–hydrophilic stretches50, 121, that tend to favour the amyloid state are commonly selected against during evolution119, 121, 122 or are otherwise neutralized by the insertion of highly aggregation-resistant residues, which are known as 'gatekeepers' (Refs 50,123). Other protective mechanisms against amyloid formation are associated with properties of the cellular environment, including the location of proteins within specific compartments124, 125, and the presence of a multitude of molecular chaperones and degradation processes, such as the ubiquitin–proteasome126, 127, 128 and the autophagy129, 130, 131 systems, which function to prevent the formation and accumulation of misfolded and aggregated polypeptide chains11, 132. Indeed, the major genetic risk factor for late-onset Alzheimer's disease is the presence of an apolipoprotein E variant that reduces the ability of cells to degrade the amyloid-β peptide133."
- matthewmcg 11y agoRight--as I understand it, it's not that different than Google's "Meeting Room Hardware Virus": "I imagine it started with all of the adapters which were thrown around in every meeting room. Everyone with a Macbook of some flavor needed a DVI to VGA adaptor in order to use the projectors, so they were plentiful. Somehow, someone probably damaged one of them and smooshed a couple of pins into places where they should not have gone. "Then, someone else forced this into their Mac. Perhaps two pins tried to go into just the one socket. At any rate, it would now break the socket and get it all out of whack. That socket, used with another adapter in another room, would then break that adapter. This new broken adapter would then go on to break even more Macbook DVI connectors. Thus, we had a hardware virus." [1] [1] https://rachelbythebay.com/w/2012/09/24/dvi/ https://rachelbythebay.com/w/2012/09/24/dvi/
- gmantom 11y agoSounds like AIDS. What with the sockets and everything.
- jotux 11y agoSimilar things happen with PCMCIA cards. The connector design on PCMCIA cards is just awful in that male pins are in the receptacle/PC. If you accidentally clog one of the holes on the PCMCIA cards connector and plug it into a receptacle it will bend the pin over.
- tropo 11y agoMale pins on the card would fail just the same way, plus they'd also get more damage from being exposed. The only upside would be easier repair and, in most cases, cheaper replacement. The correct fix would be pins with a better length/width ratio.
- TheSpiceIsLife 11y agoOr no pins as at all but rather a PCB edge connector[1]. 1. https://en.wikipedia.org/wiki/Edge_connector https://en.wikipedia.org/wiki/Edge_connector
- activee 11y agoDoes it induces a positive loop ? If does it stops when there is no more protein it can interact with ?
- Kristine1975 11y agoFrom Wikipedia as well: plants can be a vector for prions. When researchers fed hamsters grass that grew on ground where a deer that died with Chronic wasting disease (CWD) were buried, the hamsters became ill with CWD, suggesting that prions can bind to plants, which then take them up into the leaf and stem structure, where they can be eaten by herbivores, thus completing the cycle. It is thus possible that there is a progressively accumulating number of prions in the environment Are you afraid yet? ;-)