Tracking Prions

June 17, 2008

Infectious proteins known as prions have been identified as the cause of “mad cow” disease (BSE). The culprits are “incorrectly folded” proteins that can “infect” healthy proteins. The molecular bases for such prion diseases are not yet fully understood. Why are some proteins infectious while others are not?

A team headed by Beat Meier (ETH Zurich, Switzerland) and Raimon Sabaté (University of Bordeaux, France) has examined two different forms of a prion-forming protein domain by means of NMR spectroscopy. In the journal Angewandte Chemie, the researchers report that the infectious and non-infectious forms differ markedly in their molecular structure.

The word prion is derived from the term Proteinaceous Infectious Particle. These are proteins that can fold in different ways. Pathogenic prions are dangerous because they can convert physiological, non-pathogenic molecules into the diseased form. Often, prions largely consist of β-sheet structures. These are accordion-like folded protein ribbons that can easily aggregate into thread-like structures (amyloid fibrils).

The research team took on the prion-forming domain of the fungal protein HET-s. At a pH value of 7—under physiological conditions—this domain forms infectious fibrils. In acidic solution, at pH 3, it also forms fibrils, but these are not infectious.

By using nuclear magnetic resonance spectroscopy (NMR), the team was able to get a closer look at this protein. NMR allows for the evaluation of interactions of the nuclear spins of specific atomic nuclei with each other and their chemical surroundings, which gives information about the structure and dynamics of molecules and molecular fragments.

Here’s what the researchers found: The spectra of the pH 7 and pH 3 versions of the prion differ significantly. Both are mainly arranged in the rigid β-sheet structure, but up close the structures diverge widely. Particularly striking is the fact that the infectious pH 7 form has highly flexible loops in addition to the rigid domains. These are absent from the non-infectious pH 3 prions.

“The lack of infectiousness of the pH 3 fibrils is thus related to the fact that their molecular structure is significantly different from that of the fibrils formed at physiological pH,” the researchers conclude.

Citation: Beat H. Meier, Infectious and Noninfectious Amyloids of the HET-s(218–289) Prion Have Different NMR Spectra, Angewandte Chemie International Edition, doi: 10.1002/anie.200704896

Source: Angewandte Chemie

Explore further: A closer look at a deadly bacterium sets the stage for new vaccines

Related Stories

Nasty nanoinjectors pose a new target for antibiotic research

March 14, 2014

If you've ever suffered the misery of food poisoning from a bacterium like Shigella or Salmonella, then your cells have been on the receiving end of "nanoinjectors"—microscopic spikes made from proteins through which pathogens ...

Fish flu: genetics approach may lead to treatment

November 9, 2011

( -- A research team at the National Institute of Standards and Technology (NIST) has provided the first look at a genetic structure that may play a critical role in the reproduction of the infectious salmon anemia ...

Hitting moving RNA drug targets

June 26, 2011

By accounting for the floppy, fickle nature of RNA, researchers at the University of Michigan and the University of California, Irvine have developed a new way to search for drugs that target this important molecule. Their ...

3D reconstruction of a vital interaction

February 3, 2015

Researchers at IBS (CEA/CNRS/Joseph Fourier University) have succeeded for the first time in observing, on an atomic scale, the path taken and the successive changes in form undergone by a disordered vital protein, from its ...

Recommended for you

CERN collides heavy nuclei at new record high energy

November 25, 2015

The world's most powerful accelerator, the 27 km long Large Hadron Collider (LHC) operating at CERN in Geneva established collisions between lead nuclei, this morning, at the highest energies ever. The LHC has been colliding ...

The hottest white dwarf in the Galaxy

November 25, 2015

Astronomers at the Universities of Tübingen and Potsdam have identified the hottest white dwarf ever discovered in our Galaxy. With a temperature of 250,000 degrees Celsius, this dying star at the outskirts of the Milky ...

A new form of real gold, almost as light as air

November 25, 2015

Researchers at ETH Zurich have created a new type of foam made of real gold. It is the lightest form ever produced of the precious metal: a thousand times lighter than its conventional form and yet it is nearly impossible ...

Study suggests fish can experience 'emotional fever'

November 25, 2015

(—A small team of researchers from the U.K. and Spain has found via lab study that at least one type of fish is capable of experiencing 'emotional fever,' which suggests it may qualify as a sentient being. In their ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

not rated yet Jun 17, 2008
What a bunch of crap. Mad cow disease comes from feeding cows meat...a cow's digestive system is herbivoral - that is, very long. By feeding meal with meat additives inimical to the cow's health there can be no question where "mad cow disease" comes from. The same type of disease can be seen in sheep who have been fed meat. And all for a few more pounds and a few more bucks. Do you remember how many millions of animals were slaughtered in England due to Mad Cow Disease?

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.