Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Intruder detected: raise the alarm!

14.10.2011
How a molecular switch activates the anti-viral innate immune response

When a thief breaks into a bank vault, sensors are activated and the alarm is raised. Cells have their own early-warning system for intruders, and scientists at the European Molecular Biology Laboratory (EMBL) in Grenoble, France, have discovered how a particular protein sounds that alarm when it detects invading viruses.

The study, published today in Cell, is a key development in our understanding of the innate immune response, shedding light on how cells rapidly respond to a wide range of viruses including influenza, rabies and hepatitis.

To sense invading agents, cells use proteins called pattern recognition receptors, which recognise and bind to molecular signatures carried only by the intruder. This binding causes the receptors to change shape, starting a chain-reaction that ultimately alerts the surrounding cells to the invasion. How these two processes – sensing and signalling – are connected, has until now remained unclear. The EMBL scientists have now discovered the precise structural mechanism by which one of these receptors, RIG-I, converts a change of shape into a signal.

“For a structural biologist this is a classic question: how does ligand binding to a receptor induce signalling?” says Stephen Cusack, who led the work. “We were particularly interested in answering it for RIG-I, as it targets practically all RNA viruses, including influenza, measles and hepatitis C.”

In response to a viral infection, RIG-I recognises viral genetic material – specifically, viral RNA – and primes the cell to produce the key anti-viral molecule, interferon. Interferon is secreted and picked up by surrounding cells, causing them to turn on hundreds of genes that act to combat the infection. To understand how RIG-I senses only viral RNA, and not the cell’s own RNA, and sounds the alarm, the scientists used intense X-ray beams generated at the European Synchrotron Radiation Facility (ESRF) to determine the three-dimensional atomic structure of RIG-I in the presence and absence of viral RNA, in a technique called X-ray crystallography. They found that in the absence of a viral infection, the receptor is ‘sleeping with one eye open’: the part of RIG-I that senses viral RNA is exposed, whilst the domains responsible for signalling are hidden, out of reach of the signalling machinery. When RIG-I detects viral RNA, it changes shape, ‘waking up’ the signalling domains, which become accessible to trigger interferon production. Although the EMBL scientists used RIG-I from the mallard duck, this receptor’s behaviour is identical to that of its human counterpart.

“RIG-I is activated in response to viral RNA, but a similar mechanism is likely to be used by a number of other immune receptors, whether they are specific to viruses or bacteria,” says PhD student Eva Kowalinski, who carried out most of the work.

Thus, these findings contribute to a broader understanding of the workings of the innate immune system – our first line of defence against intruders, and the subject of this year’s Nobel Prize in Physiology or Medicine.

The work was carried out within the framework of the International Unit of Virus Host-Cell Interactions, a collaboration between EMBL, the University Joseph Fourier (UJF), in Grenoble, and the French Centre National de la Recherche Scientifique (CNRS) and also involved contributions from the laboratory of Denis Gerlier at the Institut National de la Santé et de la Recherche Médicale (INSERM), in Lyon, France.

Policy regarding use
EMBL press and picture releases including photographs, graphics, movies and videos are copyrighted by EMBL. They may be freely reprinted and distributed for non-commercial use via print, broadcast and electronic media, provided that proper attribution to authors, photographers and designers is made.

Sonia Furtado | EMBL Research News
Further information:
http://www.embl.org

More articles from Studies and Analyses:

nachricht ECG procedure indicates whether an implantable defibrillator will extend a patient's life
02.09.2019 | Technische Universität München

nachricht Fracking prompts global spike in atmospheric methane
14.08.2019 | European Geosciences Union

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Solving the mystery of quantum light in thin layers

A very special kind of light is emitted by tungsten diselenide layers. The reason for this has been unclear. Now an explanation has been found at TU Wien (Vienna)

It is an exotic phenomenon that nobody was able to explain for years: when energy is supplied to a thin layer of the material tungsten diselenide, it begins to...

Im Focus: An ultrafast glimpse of the photochemistry of the atmosphere

Researchers at Ludwig-Maximilians-Universitaet (LMU) in Munich have explored the initial consequences of the interaction of light with molecules on the surface of nanoscopic aerosols.

The nanocosmos is constantly in motion. All natural processes are ultimately determined by the interplay between radiation and matter. Light strikes particles...

Im Focus: Shaping nanoparticles for improved quantum information technology

Particles that are mere nanometers in size are at the forefront of scientific research today. They come in many different shapes: rods, spheres, cubes, vesicles, S-shaped worms and even donut-like rings. What makes them worthy of scientific study is that, being so tiny, they exhibit quantum mechanical properties not possible with larger objects.

Researchers at the Center for Nanoscale Materials (CNM), a U.S. Department of Energy (DOE) Office of Science User Facility located at DOE's Argonne National...

Im Focus: Novel Material for Shipbuilding

A new research project at the TH Mittelhessen focusses on the development of a novel light weight design concept for leisure boats and yachts. Professor Stephan Marzi from the THM Institute of Mechanics and Materials collaborates with Krake Catamarane, which is a shipyard located in Apolda, Thuringia.

The project is set up in an international cooperation with Professor Anders Biel from Karlstad University in Sweden and the Swedish company Lamera from...

Im Focus: Controlling superconducting regions within an exotic metal

Superconductivity has fascinated scientists for many years since it offers the potential to revolutionize current technologies. Materials only become superconductors - meaning that electrons can travel in them with no resistance - at very low temperatures. These days, this unique zero resistance superconductivity is commonly found in a number of technologies, such as magnetic resonance imaging (MRI).

Future technologies, however, will harness the total synchrony of electronic behavior in superconductors - a property called the phase. There is currently a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International Symposium on Functional Materials for Electrolysis, Fuel Cells and Metal-Air Batteries

02.10.2019 | Event News

NEXUS 2020: Relationships Between Architecture and Mathematics

02.10.2019 | Event News

Optical Technologies: International Symposium „Future Optics“ in Hannover

19.09.2019 | Event News

 
Latest News

Energy Flow in the Nano Range

18.10.2019 | Power and Electrical Engineering

MR-compatible Ultrasound System for the Therapeutic Application of Ultrasound

18.10.2019 | Medical Engineering

Double layer of graphene helps to control spin currents

18.10.2019 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>