Tinkering with a viral ribonucleotide reductase.
Ribonucleotide reductase (RNR), a crucial enzyme for nucleotide anabolism, is encoded by all living organisms and by large DNA viruses such as the herpesviruses. Surprisingly, the beta-herpesvirus subfamily RNR R1 subunit homologues are catalytically inactive and their function remained enigmatic for many years. Recent work sheds light on the function of M45, the murine cytomegalovirus R1 homologue; during viral evolution, M45 apparently lost its original RNR activity but gained the ability, via inhibiting RIP1, a cellular adaptor protein, to block cellular signaling pathways involved in innate immunity and inflammation. The discovery of this novel mechanism of viral immune subversion provides further support to the concept of evolutionary tinkering.
Lembo
David
D
Department of Clinical and Biological Sciences, University of Turin, S Luigi Gonzaga Hospital, Orbassano, Turin, Italy. david.lembo@unito.it
Brune
Wolfram
W
D000595:Amino Acid Sequence; D000818:Animals; D004247:DNA / Q000378:metabolism; D019143:Evolution, Molecular; D006564:Herpesviridae / Q000201:enzymology; D007249:Inflammation; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D018146:Muromegalovirus / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012264:Ribonucleotide Reductases / Q000737:chemistry* / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014764:Viral Proteins
D014764:Viral Proteins; D004247:DNA; D012264:Ribonucleotide Reductases