In “Cells Have Early-Warning System for Intruders” (ScienceDaily, Oct. 14, 2011), we learn:
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 October 14 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.
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.
Which all just got naturally selected, right?