| Structural highlights
Function
[L_VSIVA] RNA-directed RNA polymerase that catalyzes the transcription of viral mRNAs, their caping and polyadenylation (PubMed:24526687). The template is composed of the viral RNA tightly encapsidated by the nucleoprotein (N). The viral polymerase binds to the genomic RNA at the 3' leader promoter, and transcribes subsequently all viral mRNAs with a decreasing efficiency. The first gene is the most transcribed, and the last the least transcribed. The viral phosphoprotein acts as a processivity factor (PubMed:22908284). Caping is concommitant with initiation of mRNA transcription. The polymerase mRNA guanylyl transferase displays a different biochemical reaction than the cellular enzyme (PubMed:21945214). Polyadenylation of mRNAs occur by a stuttering mechanism at a slipery stop site present at the end viral genes. After finishing transcription of a mRNA, the polymerase can resume transcription of the downstream gene.[1] [2] [3] [4] [5] RNA-directed RNA polymerase that catalyzes the replication of viral genomic RNA. The template is composed of the viral RNA tightly encapsidated by the nucleoprotein (N). The replicase mode is dependent on intracellular N protein concentration. In this mode, the polymerase replicates the whole viral genome without recognizing transcriptional signals, and the replicated genome is not caped or polyadenylated.[6] [7] [8] [9] [PHOSP_VSIVA] Essential component of the RNA polymerase transcription and replication complex. Binds the viral ribonucleocapsid and positions the L polymerase on the template. May act as a chaperone for newly synthesized free N protein, so-called N(0). Plays a role in virion assembly.[10] [11] [12]
Publication Abstract from PubMed
The large (L) proteins of non-segmented, negative-strand RNA viruses are multifunctional enzymes that produce capped, methylated, and polyadenylated mRNA and replicate the viral genome. A phosphoprotein (P), required for efficient RNA-dependent RNA polymerization from the viral ribonucleoprotein (RNP) template, regulates the function and conformation of the L protein. We report the structure of vesicular stomatitis virus L in complex with its P cofactor determined by electron cryomicroscopy at 3.0 A resolution, enabling us to visualize bound segments of P. The contacts of three P segments with multiple L domains show how P induces a closed, compact, initiation-competent conformation. Binding of P to L positions its N-terminal domain adjacent to a putative RNA exit channel for efficient encapsidation of newly synthesized genomes with the nucleoprotein and orients its C-terminal domain to interact with an RNP template. The model shows that a conserved tryptophan in the priming loop can support the initiating 5' nucleotide.
Structure of the Vesicular Stomatitis Virus L Protein in Complex with Its Phosphoprotein Cofactor.,Jenni S, Bloyet LM, Diaz-Avalos R, Liang B, Whelan SPJ, Grigorieff N, Harrison SC Cell Rep. 2020 Jan 7;30(1):53-60.e5. doi: 10.1016/j.celrep.2019.12.024. PMID:31914397[13]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Banerjee AK, Chattopadhyay D. Structure and function of the RNA polymerase of vesicular stomatitis virus. Adv Virus Res. 1990;38:99-124. PMID:2171304
- ↑ Ogino T, Banerjee AK. An unconventional pathway of mRNA cap formation by vesiculoviruses. Virus Res. 2011 Dec;162(1-2):100-9. doi: 10.1016/j.virusres.2011.09.012. Epub, 2011 Sep 16. PMID:21945214 doi:http://dx.doi.org/10.1016/j.virusres.2011.09.012
- ↑ Morin B, Rahmeh AA, Whelan SP. Mechanism of RNA synthesis initiation by the vesicular stomatitis virus polymerase. EMBO J. 2012 Mar 7;31(5):1320-9. doi: 10.1038/emboj.2011.483. Epub 2012 Jan 13. PMID:22246179 doi:http://dx.doi.org/10.1038/emboj.2011.483
- ↑ Rahmeh AA, Morin B, Schenk AD, Liang B, Heinrich BS, Brusic V, Walz T, Whelan SP. Critical phosphoprotein elements that regulate polymerase architecture and function in vesicular stomatitis virus. Proc Natl Acad Sci U S A. 2012 Sep 4;109(36):14628-33. doi:, 10.1073/pnas.1209147109. Epub 2012 Aug 20. PMID:22908284 doi:http://dx.doi.org/10.1073/pnas.1209147109
- ↑ Morin B, Whelan SP. Sensitivity of the polymerase of vesicular stomatitis virus to 2' substitutions in the template and nucleotide triphosphate during initiation and elongation. J Biol Chem. 2014 Apr 4;289(14):9961-9. doi: 10.1074/jbc.M113.542761. Epub 2014, Feb 13. PMID:24526687 doi:http://dx.doi.org/10.1074/jbc.M113.542761
- ↑ Banerjee AK, Chattopadhyay D. Structure and function of the RNA polymerase of vesicular stomatitis virus. Adv Virus Res. 1990;38:99-124. PMID:2171304
- ↑ Morin B, Rahmeh AA, Whelan SP. Mechanism of RNA synthesis initiation by the vesicular stomatitis virus polymerase. EMBO J. 2012 Mar 7;31(5):1320-9. doi: 10.1038/emboj.2011.483. Epub 2012 Jan 13. PMID:22246179 doi:http://dx.doi.org/10.1038/emboj.2011.483
- ↑ Rahmeh AA, Morin B, Schenk AD, Liang B, Heinrich BS, Brusic V, Walz T, Whelan SP. Critical phosphoprotein elements that regulate polymerase architecture and function in vesicular stomatitis virus. Proc Natl Acad Sci U S A. 2012 Sep 4;109(36):14628-33. doi:, 10.1073/pnas.1209147109. Epub 2012 Aug 20. PMID:22908284 doi:http://dx.doi.org/10.1073/pnas.1209147109
- ↑ Morin B, Whelan SP. Sensitivity of the polymerase of vesicular stomatitis virus to 2' substitutions in the template and nucleotide triphosphate during initiation and elongation. J Biol Chem. 2014 Apr 4;289(14):9961-9. doi: 10.1074/jbc.M113.542761. Epub 2014, Feb 13. PMID:24526687 doi:http://dx.doi.org/10.1074/jbc.M113.542761
- ↑ Spadafora D, Canter DM, Jackson RL, Perrault J. Constitutive phosphorylation of the vesicular stomatitis virus P protein modulates polymerase complex formation but is not essential for transcription or replication. J Virol. 1996 Jul;70(7):4538-48. PMID:8676480
- ↑ Das SC, Pattnaik AK. Phosphorylation of vesicular stomatitis virus phosphoprotein P is indispensable for virus growth. J Virol. 2004 Jun;78(12):6420-30. PMID:15163735 doi:http://dx.doi.org/10.1128/JVI.78.12.6420-6430.2004
- ↑ Das SC, Pattnaik AK. Role of the hypervariable hinge region of phosphoprotein P of vesicular stomatitis virus in viral RNA synthesis and assembly of infectious virus particles. J Virol. 2005 Jul;79(13):8101-12. PMID:15956555 doi:http://dx.doi.org/10.1128/JVI.79.13.8101-8112.2005
- ↑ Jenni S, Bloyet LM, Diaz-Avalos R, Liang B, Whelan SPJ, Grigorieff N, Harrison SC. Structure of the Vesicular Stomatitis Virus L Protein in Complex with Its Phosphoprotein Cofactor. Cell Rep. 2020 Jan 7;30(1):53-60.e5. doi: 10.1016/j.celrep.2019.12.024. PMID:31914397 doi:http://dx.doi.org/10.1016/j.celrep.2019.12.024
|
