2PGG

The structure of a birnavirus polymerase reveals a distinct active site topology.

(2007) Proc Natl Acad Sci U S A 104: 7385-7390

• PubMed: 17456597 Search on PubMedSearch on PubMed Central
• DOI: https://doi.org/10.1073/pnas.0611599104
• Primary Citation of Related Structures:  
  2PGG


• PubMed Abstract: 
  

  Single-subunit polymerases are universally encoded in both cellular organisms and viruses. Their three-dimensional structures have the shape of a right-hand with the active site located in the palm region, which has a topology similar to that of the RNA recognition motif (RRM) found in many RNA-binding proteins. Considering that polymerases have well conserved structures, it was surprising that the RNA-dependent RNA polymerases from birnaviruses, a group of dsRNA viruses, have their catalytic motifs arranged in a permuted order in sequence. Here we report the 2.5 A structure of a birnavirus VP1 in which the polymerase palm subdomain adopts a new active site topology that has not been previously observed in other polymerases. In addition, the polymerase motif C of VP1 has the sequence of -ADN-, a highly unusual feature for RNA-dependent polymerases. Through site-directed mutagenesis, we have shown that changing the VP1 motif C from -ADN- to -GDD- results in a mutant with an increased RNA synthesis activity. Our results indicate that the active site topology of VP1 may represent a newly developed branch in polymerase evolution, and that birnaviruses may have acquired the -ADN- mutation to control their growth rate.

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Organizational Affiliation: 

Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77005, USA.