Mechanism for coordinated RNA packaging and genome replication by rotavirus polymerase VP1.
Publication Type:Journal Article
Source:Structure, Volume 16, Issue 11, p.1678-88 (2008)
Keywords:Apoenzymes, Base Sequence, Binding Sites, DNA-Directed RNA Polymerases, Models, Molecular, Nucleic Acid Conformation, Oligoribonucleotides, Protein Conformation, RNA, Viral, Rotavirus
<p>Rotavirus RNA-dependent RNA polymerase VP1 catalyzes RNA synthesis within a subviral particle. This activity depends on core shell protein VP2. A conserved sequence at the 3' end of plus-strand RNA templates is important for polymerase association and genome replication. We have determined the structure of VP1 at 2.9 A resolution, as apoenzyme and in complex with RNA. The cage-like enzyme is similar to reovirus lambda3, with four tunnels leading to or from a central, catalytic cavity. A distinguishing characteristic of VP1 is specific recognition, by conserved features of the template-entry channel, of four bases, UGUG, in the conserved 3' sequence. Well-defined interactions with these bases position the RNA so that its 3' end overshoots the initiating register, producing a stable but catalytically inactive complex. We propose that specific 3' end recognition selects rotavirus RNA for packaging and that VP2 activates the autoinhibited VP1/RNA complex to coordinate packaging and genome replication.</p>