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.
“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.0060006CONTACT:
Andrew Hyde | alfa
Decoding the genome's cryptic language
27.02.2017 | University of California - San Diego
New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg
On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded after a glide flight with an Airbus A320 in ditching on the Hudson River. All 155 people on board were saved.
On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded...
Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...
The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.
The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...
Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...
13.02.2017 | Event News
10.02.2017 | Event News
09.02.2017 | Event News
27.02.2017 | Materials Sciences
27.02.2017 | Interdisciplinary Research
27.02.2017 | Life Sciences