Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

From good to bad with a copper switch

20.10.2015

Here's the mechanism that creates prions, the 'bad' proteins

At the molecular level, the difference between Doctor Jekyll and Mr Hyde lies in a metal, copper. In its physiological form, the prion protein (PrPC ) is 'good' and is involved in normal body processes. It can happen, however, that because of some as yet unknown mechanism, it changes form and turns into a threat for the health of humans and animals (it is responsible for neurodegenerative diseases such as spongiform encephalopathies).


This is a photograph showing how PrPC turns into a Prion.

Credit: SISSA

According to a new SISSA study, the mechanism underlying this change is a metal, copper, or rather a particular region of the protein to which the metal binds, which acts as a sort of 'switch' that turns PrPC into its terrible alter ego.

"We still don't know what complex molecular mechanisms cause the prion protein to become bad," explains Giuseppe Legname, professor at the International School for Advanced Studies (SISSA) in Trieste who coordinated the new study, "nor do we know any treatments to cure prion diseases. Our research has finally uncovered a critical cofactor, which is capable of triggering the transformation of prions proteins from good to bad. And this cofactor is copper which binds to an amino acid sequence of the prion protein, known as 'fifth copper binding site', which has so far been poorly studied".

"In physiological conditions, copper is tightly bound to two histidine amino acids", continues Legname. "When copper is bound in this way it seems to protect the prion protein. When instead copper is missing or is bound to one rather than two histidines, that's when problems arise: the prion protein becomes unstable and turns into a bad and infectious prion".

To reach this conclusion, the researchers used multidisciplinary experimental approaches, ranging from structural to cellular biology. "It all started with an intuition we published in the journal Biochemistry in 2012", explains Gabriele Giachin, first author of the study and former SISSA PhD student (today at the European Synchrotron Radiation Facility, ESRF, in Grenoble, France).

"On that occasion, we hypothesized that the pathological genetic mutations present in the prion protein could affect copper coordination". Starting from this intuition, Giachin and colleagues went on to conduct in-depth experiments using XAFS (X-ray absorption fine structure) spectroscopy, exploiting the powerful X-rays available at the Grenoble synchrotron. Then, drawing on the consolidated expertise in molecular and cellular biology available at the SISSA Laboratory of Prion Biology coordinated by Legname, the group confirmed the hypothesis in living cell systems.

"These results finally answer a fundamental question: what mechanism underlies the appearance of prions?", concludes Legname. "We have been the first to provide a detailed description of the role of copper in prion conversion, opening the way for the development of new drugs targeting this copper binding site, and thus for new potential treatments".

###

The study was conducted through the collaboration of a group of SISSA scientists (in addition to Giachin and Legname, the group includes Thao Mai, Thanh Hoa Tran, Giulia Salzano and Federico Benetti) and a group coordinated by the University of Rome "La Sapienza", led by Paola D'Angelo.

Prion proteins and prions Prions are proteins that have undergone a change in structure from a physiological "good" form normally present in our brain to an aberrant (or "bad") form capable of causing degeneration of nervous tissue and diseases, some of which very severe. Among the diseases are Creutzfeld Jakob disease in humans and "mad cow" disease in cattle. Unique in nature, prions can also be infectious, like viruses and bacteria, in that they can be transmitted between individuals of the same or even different species.

Media Contact

Federica Sgorbissa
pressoffice@sissa.it
39-040-378-7644

 @sissaschool

http://www.sissa.it 

Federica Sgorbissa | EurekAlert!

Further reports about: COPPER SISSA amino cellular biology prion protein prions structure

More articles from Health and Medicine:

nachricht Millions through license revenues
27.04.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>