Lu, XiaohuiMcDonald, Sarah M.Tortorici, M. AlejandraTao, Yizhi JaneCarpio, Rodrigo Vasquez-DelNibert, MaxPatton, John T.Harrison, Stephen2011-02-092008Lu, Xiaohui, Sarah M. McDonald, M. Alejandra Tortorici, Yizhi Jane Tao, Rodrigo Vasquez-Del Carpio, Max L. Nibert, John T. Patton, and Stephen C. Harrison. 2008. Mechanism for coordinated RNA packaging and genome replication by rotavirus polymerase VP1. Structure 16(11): 1678-1688.0969-2126http://nrs.harvard.edu/urn-3:HUL.InstRepos:4723679Rotavirus 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 plusstrand RNA templates is important for polymerase association and genome replication. We have determined the structure of VP1 at 2.9 Å resolution, as apoenzyme and in complex with RNA. The cage-like enzyme is similar to reovirus λ3, 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 auto-inhibited VP1/RNA complex to coordinate packaging and genome replication.en-USJournal Article2011-02-0910.1016/j.str.2008.09.006