Browsing by Author "Pan, Junhua"

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    Structural and functional studies of birnavirus RNA polymerases---Insights into the protein-priming mechanism and the evolution of RNA viruses
    (2008) Pan, Junhua; Tao, Yizhi Jane
    The first crystal structure of a birnavirus polymerase, IBDV VP1, has been determined at 2.5 A resolution by multiple isomorphous replacement and anomalous scattering (MIR-AS). The VP1 structure reveals several highly unusual features. By adopting a novel topology in the polymerase palm subdomain, VP1 is able to bring several functional motifs into spatial proximity to form a complete polymerase active site, despite the permutaion of sequence. By modeling initiation and elongation complexes onto the VP1 structure, important structural features are demonstrated and insights into the functions of the birnavirus self-guanylylation and protein-primed RNA synthesis are presented. Both self-guanylylation and nucleotide polymerization activities of VP1 are explored using various biochemical approaches; and based on the combination these findings and site-directed mutagenesis, speculations about the mechanisms of the self-guanylylation active site and the unusual polymerase active site are presented. Moreover, the VP1 structure lends further support for the evolutionary relationship between dsRNA and +ssRNA viruses. Progress in crystallographic and functional studies on other birnavirus polymerases and various functional complexes are also provided for the future direction of further investigation on the structural basis of the protein-priming mechanism by birnavirus VP1.