Prompting Prions

Credit: © Russell Kightley / The paper: Deleault et al., "Formation of native prions from minimal components in vitro,"

By | April 1, 2009

<figcaption> Credit: © Russell Kightley /</figcaption>
Credit: © Russell Kightley /

The paper:

Deleault et al., "Formation of native prions from minimal components in vitro," Proc Natl Acad Sci, 104: 9741-6, 2007. (Cited in 53 papers)

The finding:

To test whether misfolded, disease-causing prion proteins could form from their normal counterparts without being seeded with the infectious form, biochemist Surachai Supattapone and his colleagues at Dartmouth Medical School in Hanover, NH, mixed a cocktail of purified, uninfectious prions, a synthetic, highly charged RNA, and some lipids. After stirring the concoction with sound waves, the normal proteins morphed into their lethal cousins and triggered scrapie—a fatal prion disease—when injected into hamsters.

The impact:

The study was the first showing that fully infectious proteins can be created from scratch, "even without adding any infectious material in the reaction," says Ilia Baskakov, a biochemist at the University of Maryland Biotechnology Institute in Baltimore. "It's one of the milestones in the field."

The follow-up:

In 2007, Supattapone's team used fluorescent labeling to show that the highly charged RNA molecule physically incorporates into the misfolded, infectious prion after the sonic treatment (J Biol Chem 82:36341-53, 2007).

The next step:

Supattapone's team is now working to discover the naturally occurring cofactors that make the good proteins go bad. "If we can remove the cofactor molecule from the infectious agent," he says, "how will that affect the infectivity of the final product?"

CocktailHamsters with scrapieMean time until symptoms
Normal protein alone (PrPC)0/5>370 days
RNA + PrPC without amplification0/6>360 days
RNA + PrPC with amplification7/8134 days


Avatar of: Steven Brenner

Steven Brenner

Posts: 14

March 31, 2009

If the prion protein becomes dysfunctional by charged RNA, then is cellular function impaired by loss of prion protein function. Apparently it has been found to be a copper transporter and also is involved in normal beta-amyloid function in Alzheimer disease since if prion protein is not interacting properly with lipid rafts in the cell membrane, toxic beta-amyloid is produced, apparently leading to Alzheimer disease in the brain.
Avatar of: anonymous poster

anonymous poster

Posts: 125

April 9, 2009

It probably does, as too many things in our body serve more than one purpose, including opposing functions at different circumstances. Even the so-called "death" agents (e.g., Bax/Bak, cytochrome c) are now known to serve vital functions in healthy cells.

Popular Now

  1. 2017 Top 10 Innovations
    Features 2017 Top 10 Innovations

    From single-cell analysis to whole-genome sequencing, this year’s best new products shine on many levels.

  2. Thousands of Mutations Accumulate in the Human Brain Over a Lifetime
  3. Antiviral Immunotherapy Comes of Age
    News Analysis Antiviral Immunotherapy Comes of Age

    T-cell therapies are not just for cancer. Researchers are also advancing immunotherapy methods to protect bone marrow transplant patients from viral infections. 

  4. Search for Life on the Red Planet