Naked Science Forum
Life Sciences => Cells, Microbes & Viruses => Topic started by: Jesse on 06/01/2010 10:30:02
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Jesse asked the Naked Scientists:
Hey Naked Scientists,
Can any of my proteins randomly, accidentally become a prion, without contact with any other prions?
Thanks!
Jesse
What do you think?
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Prions are misfolded versions of the brain protein PrP. So it seems to be a specific protein?
--Quotes--
Studying yeast proteins, a pair of researchers at the Massachusetts Institute of Technology's Whitehead Institute of Biomedical Research discovered that a highly specific section of a prion protein's amino-acid sequence controls its switch to the prion state. In addition, this same segment regulates its ability to cross species barriers...
The scientists worked with Sup35, a protein that is normally responsible for stopping the translation of messenger RNA (mRNA) into other proteins, but has the ability to readily shift into a prion state. When the researchers incubated full strands of Sup35 in its nonprion state with the array of peptides, they found that a certain section of the peptides, encompassing about 10 percent of an entire protein sequence, served as a "recognition element," which bound the Sup35 protein and caused it to begin folding into its prion state. This then initiated a conformational cascade...
In the classic sense, prions, which are misfolded versions of the brain protein PrP, cannot mutate because they do not contain DNA or RNA. They can, however, give rise to variants with different properties, possibly due to differences in the folding, or shape, of the proteins. In the study, published December 31 in Science Express, researchers estimated the rate at which prion mutants can appear in cultured human nerve cells. In addition, the study suggests that once variants appear, they persist at low levels, giving rise to a heterogeneous prion population. "On the face of it, you have exactly the same process of mutation and adaptive change in prions as you see in viruses,"
The fact that new prion "substrains" can appear and spread among cells in just a couple dozen cell divisions suggests that drug-resistance could easily develop in the lifetime of the host, from mouse to man. As a result, therapeutic attempts to inhibit the prion form of PrP are "likely to be thwarted," the authors wrote...Different groups are pursuing the possibility of silencing the PrP gene or using antibodies that bind normal PrP protein as a treatment for prion disease.
New research, led by scientists at NIAID’s Rocky Mountain Laboratories (RML) in Hamilton, MT, reveals that the most infectious prions are significantly smaller than the large thread-like deposits of PrP molecules readily seen in the diseased brains of infected individuals. Yet to be infectious, a prion must be much larger than the single malformed PrP molecule that has long been thought to be the basic unit of infectivity.
Prions appear to be crystal-like clusters of PrP molecules that can grab normal, dissolved PrP molecules and convert them to a solid, crystal-like state, says RML senior researcher Byron Caughey, Ph.D. “Although large prion particles can do this, and are infectious, you can infect many more individuals, or cause much more rapid disease in a single individual, with an equivalent weight of small prion particles,” says Dr. Caughey. “But our findings also suggest that if the PrP cluster is smaller than a certain minimum size, it becomes unstable and loses its infectious properties.”
Normal PrP molecules found in many animals do not cause harm. But PrP molecules can become lethal and destroy the brain when they refold and gather into precisely ordered clusters. This basic infectious process is reminiscent of disease processes seen with other prominent neurological diseases, except that in each disease a different protein is involved.
--End of quotes-- From.
Mad Cow Disease_1 (http://www.scientificamerican.com/article.cfm?id=prion-formation-behind-mad-cow-disease) and Mad Cow Disease_2. (http://www.scientificamerican.com/blog/post.cfm?id=prion-evolution-takes-lessons-on-di-2010-01-01) And lastly this. (http://www3.niaid.nih.gov/news/newsreleases/2005/Caughey.htm)