Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Unique Role of Cell Death Protein TRADD in Viral Signaling

15.01.2008
Epstein-Barr virus is incredibly common in humans; up to 95% of adults in the developed world have been infected, which causes glandular fever and has been linked to the development of several forms of cancer. Research published in this week’s PLoS Biology investigates the way that the virus manipulates TRADD—a human protein—in order to establish itself in the host.

Epstein-Barr virus alters the way cells in the human immune system, called B lymphocytes, behave, transforming them into cancerous cells that survive and divide more than they should. It seems strange that TRADD can be involved in transforming cells to do this, because in a healthy person, TRADD is important in doing just the opposite: it causes apoptosis—organized cell death.

Researchers based in the GSF – National Research Centre for Environment and Health (from 2008: Helmholtz Zentrum Muenchen), in Munich, studied the way that TRADD interacts with LMP1, a protein produced by the virus that is essential for cell transformation. They genetically altered cells so that they wouldn’t produce any TRADD and found that these cells didn’t respond to the transformation signals sent by the LMP1 protein, showing that TRADD is necessary for this change. They studied the shape of the viral protein LMP1, and showed that a region of it binds to TRADD in a unique way. When TRADD is bound to LMP1, it is unable to interact with the molecules that it normally would, and so it cannot cause cell death as it is meant to.

The researchers, led by Dr. Arnd Kieser, took the unique TRADD binding site that they had identified on the viral protein and used it to replace the TRADD binding site on the host cellular protein that mediates cell death. This was enough to convert the cellular protein into a non-apoptotic receptor and thus to stop TRADD from inducing apoptosis. This is excellent evidence that they have correctly identified the mechanism that the viral protein uses to transform B lymphocytes.

... more about:
»LMP1 »Syn »TRADD »formation

“It is amazing to learn which sophisticated molecular means this human tumor virus has developed to take control of the communication system of its host cell,” Kieser said. “The unique interaction of LMP1 with TRADD could serve as a target structure for drug development against EBV-induced cancers.”

Conformational Equilibria in Monomeric a-Synuclein at the Single-Molecule Level

Natively unstructured proteins defy the classical “one sequence-one structure” paradigm of protein science. In pathological conditions, monomers of these proteins can aggregate in the cell, a process that underlies neurodegenerative diseases such as Alzheimer and Parkinson. A key step in the aggregation process, the formation of misfolded intermediates, remains obscure. This week in the open-access online journal PLoS Biology, researchers Luigi Bubacco, Bruno Samori and colleagues characterized the folding and conformational diversity of ?Syn, a natively unstructured protein involved in Parkinson disease, by mechanically stretching single molecules of this protein and recording their mechanical properties. These experiments permitted them to directly observe and quantify three main classes of conformations that, under in vitro physiological conditions, exist simultaneously in the ?Syn sample. They found that one class of conformations, “?-like” structures, is directly related to ?Syn aggregation. In fact, their relative abundance increases drastically in three different conditions known to promote the formation of ?Syn fibrils. They expect that a critical concentration of ?Syn with a “?-like” structure must be reached to trigger fibril formation. This critical concentration is therefore controlled by a chemical equilibrium. Novel pharmacological strategies can now be tailored to act upstream, before the aggregation process ensues, by targeting this equilibrium. To this end, Single Molecule Force Spectroscopy can be an effective tool to tailor and test new pharmacological agents.

Citation: Sandal M, Valle F, Tessari I, Mammi S, Bergantino E, et al. (2008) Conformational equilibria in monomeric a-synuclein at the single-molecule level. PLoS Biol 6(1): e6.doi:10.1371/journal.pbio.0060006

CONTACT:
Bruno Samori
University of Bologna
Department of Biochemistry
Bologna, 40126
Italy
+39 05 12 09 43 87
bruno.samori@unibo.it

Andrew Hyde | alfa
Further information:
http://www.plosbiology.org
http://biology.plosjournals.org/perlserv/?request=get- document&doi=10.1371/journal.pbio.0060006

Further reports about: LMP1 Syn TRADD formation

More articles from Life Sciences:

nachricht Bolstering fat cells offers potential new leukemia treatment
17.10.2017 | McMaster University

nachricht Ocean atmosphere rife with microbes
17.10.2017 | King Abdullah University of Science & Technology (KAUST)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Ocean atmosphere rife with microbes

17.10.2017 | Life Sciences

Neutrons observe vitamin B6-dependent enzyme activity useful for drug development

17.10.2017 | Life Sciences

NASA finds newly formed tropical storm lan over open waters

17.10.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>