Cracking a virus protect...( gh-resolution image of the protein....)

"Nucleoprotein acts like a clamp," says Weissenhorn. "It consists of two domains that like two jaws clasp around the RNA strand. Many nucleoproteins bind side-by-side along the length of an RNA molecule and make it inaccessible for degrading enzymes but also for the machinery needed to replicate the virus. This means that the protection shield must be flexible and able to distinguish between different types of enzymes trying to gain access."

The detailed structural picture suggests that upon a signal a part of the protein located between the two main domains might act as a hinge that moves the upper jaw out of the way when time for replication has come.

"This dynamic mechanism makes nucleoproteins an excellent drug target," says Ruigrok, "Small agents that bind to the protein in such a way to block its flexibility and keep it in the closed state, would prevent replication of the virus and would stop it from spreading."

Rabies virus shares this protection strategy with other viruses of its class; in Ebola, measles and Borna virus similar complexes of RNA and nucleoproteins have been found.

"This means that our results do not only have implications for the design of new drugs against rabies, but they suggest new therapeutic approaches in a variety of diseases, some of which are much more threatening than rabies. On a different note, the conservation of the nucleoprotein system also leaves room for evolutionary speculations about common ancestors and primordial infectious units of RNA viruses," Weissenhorn concludes.

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Contact: Anna-Lynn Wegener
wegener@embl.de
49-622-138-7452
European Molecular Biology Laboratory
16-Jun-2006