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Molecular Arms Race

 
  December, 10 2008 19:41
your information resource in human molecular genetics
 
     
A key immunity-related protein evolved quickly in a molecular 'arms race' with poxviruses, a Nature paper suggests. It is thought that the strategy helps host stay ahead of pathogen.

Poxviruses, such as smallpox, produce a protein called K3L, which closely mimics the substrate of protein kinase R (PKR), an important component of vertebrate immunity. Nels Elde and colleagues show that PKR evolved under dramatic episodes of positive selection in primates, substituting amino acids at sites where K3L and PKR meet. The changes increase the probability of the host defeating the mimic and see the two protagonists locked in a molecular 'arms race', each trying to gain the upper hand.

In a related paper published online in Nature Structural & Molecular Biology, Stefan Rothenburg and colleagues provide evidence for poxvirus-driven evolution of PKR in vertebrates. They show that substituting a single amino acid in mouse PKR with the amino acid found at the same position in human PKR renders mouse PKR more resistant to K3L. The research demonstrates how an antiviral protein has evolved to avoid being deactivated by the virus, while maintaining its primary function.

Author contacts:

Nels Elde (Fred Hutchinson Cancer Research Center, Seattle, WA, USA)
E-mail: nelde@fhcrc.org Author - Nature paper

Stefan Rothenburg (National Institute of Child Health and Human Development, Bethesda, MD, USA)
E-mail: rothenst@mail.nih.gov Author - NSMB paper

Abstracts available online:
Nature paper Abstract.
NSMB paper Abstract.

(C) Nature press release.


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