4f5x

Structural highlights

Function

[RDRP_ROTSP] RNA-directed RNA polymerase that is involved in both transcription and genome replication. Together with VP3 capping enzyme, forms an enzyme complex positioned near the channels situated at each of the five-fold vertices of the core. Following infection, the outermost layer of the virus is lost, leaving a double-layered particle (DLP) made up of the core and VP6 shell. VP1 then catalyzes the transcription of fully conservative plus-strand genomic RNAs that are extruded through the DLP's channels into the cytoplasm where they function as mRNAs for translation of viral proteins. One copy of each of the viral (+)RNAs is also recruited during core assembly, together with newly synthesized polymerase complexes and VP2. The polymerase of these novo-formed particles catalyzes the synthesis of complementary minus-strands leading to dsRNA formation. To do so, the polymerase specifically recognizes and binds 4 bases 5'-UGUG-3' in the conserved 3'-sequence of plus-strand RNA templates. VP2 presumably activates the autoinhibited VP1-RNA complex to coordinate packaging and genome replication. Once dsRNA synthesis is complete, the polymerase switches to the transcriptional mode, thus providing secondary transcription.^{[1] [2]} [VP6_ROTBN] Intermediate capsid protein that self assembles to form an icosahedral capsid with a T=13 symmetry, which consists of 230 trimers of VP6, with channels at each of its five-fold vertices. This capsid constitutes the middle concentric layer of the viral mature particle. The innermost VP2 capsid and the intermediate VP6 capsid remain intact following cell entry to protect the dsRNA from degradation and to prevent unfavorable antiviral responses in the host cell during all the replication cycle of the virus. Nacent transcripts are transcribed within the structural confines of this double-layered particle (DLP) and are extruded through the channels at the five-fold axes. VP6 is required for the transcription activity of the DLP (By similarity).

See Also

• RNA polymerase 3D structures

References

1. ↑ Patton JT, Jones MT, Kalbach AN, He YW, Xiaobo J. Rotavirus RNA polymerase requires the core shell protein to synthesize the double-stranded RNA genome. J Virol. 1997 Dec;71(12):9618-26. PMID:9371626
2. ↑ Lu X, McDonald SM, Tortorici MA, Tao YJ, Vasquez-Del Carpio R, Nibert ML, Patton JT, Harrison SC. Mechanism for coordinated RNA packaging and genome replication by rotavirus polymerase VP1. Structure. 2008 Nov 12;16(11):1678-88. PMID:19000820 doi:10.1016/j.str.2008.09.006
3. ↑ Estrozi LF, Settembre EC, Goret G, McClain B, Zhang X, Chen JZ, Grigorieff N, Harrison SC. Location of the dsRNA-Dependent Polymerase, VP1, in Rotavirus Particles. J Mol Biol. 2012 Oct 23. pii: S0022-2836(12)00829-7. doi:, 10.1016/j.jmb.2012.10.011. PMID:23089332 doi:http://dx.doi.org/10.1016/j.jmb.2012.10.011