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
Sonia Furtado | EMBL Research News
Deep Brain Stimulation Provides Sustained Relief for Severe Depression
19.03.2019 | Universitätsklinikum Freiburg
AI study of risk factors in type 1 diabetes
06.03.2019 | University of Gothenburg
Cancers that display a specific combination of sugars, called T-antigen, are more likely to spread through the body and kill a patient. However, what regulates...
DESY and MPSD scientists create high-order harmonics from solids with controlled polarization states, taking advantage of both crystal symmetry and attosecond electronic dynamics. The newly demonstrated technique might find intriguing applications in petahertz electronics and for spectroscopic studies of novel quantum materials.
The nonlinear process of high-order harmonic generation (HHG) in gases is one of the cornerstones of attosecond science (an attosecond is a billionth of a...
Nano- and microtechnology are promising candidates not only for medical applications such as drug delivery but also for the creation of little robots or flexible integrated sensors. Scientists from the Max Planck Institute for Polymer Research (MPI-P) have created magnetic microparticles, with a newly developed method, that could pave the way for building micro-motors or guiding drugs in the human body to a target, like a tumor. The preparation of such structures as well as their remote-control can be regulated using magnetic fields and therefore can find application in an array of domains.
The magnetic properties of a material control how this material responds to the presence of a magnetic field. Iron oxide is the main component of rust but also...
Due to the special arrangement of its molecules, a new coating made of corn starch is able to repair small scratches by itself through heat: The cross-linking via ring-shaped molecules makes the material mobile, so that it compensates for the scratches and these disappear again.
Superficial micro-scratches on the car body or on other high-gloss surfaces are harmless, but annoying. Especially in the luxury segment such surfaces are...
The Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI) at the Large Binocular Telescope (LBT) in Arizona released its first image of the surface magnetic field of another star. In a paper in the European journal Astronomy & Astrophysics, the PEPSI team presents a Zeeman- Doppler-Image of the surface of the magnetically active star II Pegasi.
A special technique allows astronomers to resolve the surfaces of faraway stars. Those are otherwise only seen as point sources, even in the largest telescopes...
11.03.2019 | Event News
01.03.2019 | Event News
28.02.2019 | Event News
26.03.2019 | Physics and Astronomy
26.03.2019 | Earth Sciences
26.03.2019 | Earth Sciences