| Structural highlights
Function
[MCEL_VACCW] Catalytic subunit of the mRNA capping enzyme which catalyzes three enzymatic reactions: the 5' triphosphate end of the pre-mRNA is hydrolyzed to a diphosphate by RNA 5' triphosphatase; the diphosphate RNA end is capped with GMP by RNA guanylyltransferase and the GpppN cap is methylated by RNA (guanine-N7) methyltransferase. Heterodimeric mRNA capping enzyme catalyzes the linkage of a N7-methyl-guanosine moiety to the first transcribed nucleotide (cap 0 structure), whereas the polymerase associated VP39 is responsible for a second methylation at the 2'-O position of the ribose (cap 1 structure).[1] [2] [3] The heterodimeric enzyme is also involved in early viral gene transcription termination and intermediate viral gene transcription initiation. Early gene transcription termination requires the termination factor VTF, the DNA-dependent ATPase NPH-I and the Rap94 subunit of the viral RNA polymerase, as well as the presence of a specific termination motif. Binds, together with RAP94, to the termination motif 5'-UUUUUNU-3' in the nascent early mRNA.[4] [5] [6] [MCES_VACCW] Regulatory subunit of the mRNA cap enzyme which stabilizes the catalytic subunit and enhances its methyltransferase activity through an allosteric mechanism. Heterodimeric mRNA capping enzyme catalyzes the linkage of a N7-methyl-guanosine moiety to the first transcribed nucleotide (cap 0 structure), whereas the polymerase associated VP39 is responsible for a second methylation at the 2'-O position of the ribose (cap 1 structure).[7] [8] [9] The heterodimeric enzyme is also involved in early viral gene transcription termination and intermediate viral gene transcription initiation. Early gene transcription termination requires the termination factor VTF, the DNA-dependent ATPase NPH-I and the Rap94 subunit of the viral RNA polymerase, as well as the presence of a specific termination motif. Binds, together with RAP94, to the termination motif 5'-UUUUUNU-3' in the nascent early mRNA.[10] [11] [12]
Publication Abstract from PubMed
Vaccinia virus capping enzyme is a heterodimer of D1 (844 aa) and D12 (287 aa) polypeptides that executes all three steps in m(7)GpppRNA synthesis. The D1 subunit comprises an N-terminal RNA triphosphatase (TPase)-guanylyltransferase (GTase) module and a C-terminal guanine-N7-methyltransferase (MTase) module. The D12 subunit binds and allosterically stimulates the MTase module. Crystal structures of the complete D1D12 heterodimer disclose the TPase and GTase as members of the triphosphate tunnel metalloenzyme and covalent nucleotidyltransferase superfamilies, respectively, albeit with distinctive active site features. An extensive TPase-GTase interface clamps the GTase nucleotidyltransferase and OB-fold domains in a closed conformation around GTP. Mutagenesis confirms the importance of the TPase-GTase interface for GTase activity. The D1D12 structure complements and rationalizes four decades of biochemical studies of this enzyme, which was the first capping enzyme to be purified and characterized, and provides new insights into the origins of the capping systems of other large DNA viruses.
Crystal structure of vaccinia virus mRNA capping enzyme provides insights into the mechanism and evolution of the capping apparatus.,Kyrieleis OJ, Chang J, de la Pena M, Shuman S, Cusack S Structure. 2014 Mar 4;22(3):452-65. doi: 10.1016/j.str.2013.12.014. PMID:24607143[13]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Shatzer AN, Kato SE, Condit RC. Phenotypic analysis of a temperature sensitive mutant in the large subunit of the vaccinia virus mRNA capping enzyme. Virology. 2008 May 25;375(1):236-52. doi: 10.1016/j.virol.2008.01.028. Epub 2008 , Mar 4. PMID:18295814 doi:http://dx.doi.org/10.1016/j.virol.2008.01.028
- ↑ Christen LA, Piacente S, Mohamed MR, Niles EG. Vaccinia virus early gene transcription termination factors VTF and Rap94 interact with the U9 termination motif in the nascent RNA in a transcription ternary complex. Virology. 2008 Jun 20;376(1):225-35. doi: 10.1016/j.virol.2008.03.031. Epub 2008 , May 1. PMID:18455214 doi:http://dx.doi.org/10.1016/j.virol.2008.03.031
- ↑ Zheng S, Shuman S. Structure-function analysis of vaccinia virus mRNA cap (guanine-N7) methyltransferase. RNA. 2008 Apr;14(4):696-705. doi: 10.1261/rna.928208. Epub 2008 Feb 6. PMID:18256245 doi:http://dx.doi.org/10.1261/rna.928208
- ↑ Shatzer AN, Kato SE, Condit RC. Phenotypic analysis of a temperature sensitive mutant in the large subunit of the vaccinia virus mRNA capping enzyme. Virology. 2008 May 25;375(1):236-52. doi: 10.1016/j.virol.2008.01.028. Epub 2008 , Mar 4. PMID:18295814 doi:http://dx.doi.org/10.1016/j.virol.2008.01.028
- ↑ Christen LA, Piacente S, Mohamed MR, Niles EG. Vaccinia virus early gene transcription termination factors VTF and Rap94 interact with the U9 termination motif in the nascent RNA in a transcription ternary complex. Virology. 2008 Jun 20;376(1):225-35. doi: 10.1016/j.virol.2008.03.031. Epub 2008 , May 1. PMID:18455214 doi:http://dx.doi.org/10.1016/j.virol.2008.03.031
- ↑ Zheng S, Shuman S. Structure-function analysis of vaccinia virus mRNA cap (guanine-N7) methyltransferase. RNA. 2008 Apr;14(4):696-705. doi: 10.1261/rna.928208. Epub 2008 Feb 6. PMID:18256245 doi:http://dx.doi.org/10.1261/rna.928208
- ↑ Niles EG, Lee-Chen GJ, Shuman S, Moss B, Broyles SS. Vaccinia virus gene D12L encodes the small subunit of the viral mRNA capping enzyme. Virology. 1989 Oct;172(2):513-22. PMID:2552660
- ↑ Shatzer AN, Kato SE, Condit RC. Phenotypic analysis of a temperature sensitive mutant in the large subunit of the vaccinia virus mRNA capping enzyme. Virology. 2008 May 25;375(1):236-52. doi: 10.1016/j.virol.2008.01.028. Epub 2008 , Mar 4. PMID:18295814 doi:http://dx.doi.org/10.1016/j.virol.2008.01.028
- ↑ Christen LA, Piacente S, Mohamed MR, Niles EG. Vaccinia virus early gene transcription termination factors VTF and Rap94 interact with the U9 termination motif in the nascent RNA in a transcription ternary complex. Virology. 2008 Jun 20;376(1):225-35. doi: 10.1016/j.virol.2008.03.031. Epub 2008 , May 1. PMID:18455214 doi:http://dx.doi.org/10.1016/j.virol.2008.03.031
- ↑ Niles EG, Lee-Chen GJ, Shuman S, Moss B, Broyles SS. Vaccinia virus gene D12L encodes the small subunit of the viral mRNA capping enzyme. Virology. 1989 Oct;172(2):513-22. PMID:2552660
- ↑ Shatzer AN, Kato SE, Condit RC. Phenotypic analysis of a temperature sensitive mutant in the large subunit of the vaccinia virus mRNA capping enzyme. Virology. 2008 May 25;375(1):236-52. doi: 10.1016/j.virol.2008.01.028. Epub 2008 , Mar 4. PMID:18295814 doi:http://dx.doi.org/10.1016/j.virol.2008.01.028
- ↑ Christen LA, Piacente S, Mohamed MR, Niles EG. Vaccinia virus early gene transcription termination factors VTF and Rap94 interact with the U9 termination motif in the nascent RNA in a transcription ternary complex. Virology. 2008 Jun 20;376(1):225-35. doi: 10.1016/j.virol.2008.03.031. Epub 2008 , May 1. PMID:18455214 doi:http://dx.doi.org/10.1016/j.virol.2008.03.031
- ↑ Kyrieleis OJ, Chang J, de la Pena M, Shuman S, Cusack S. Crystal structure of vaccinia virus mRNA capping enzyme provides insights into the mechanism and evolution of the capping apparatus. Structure. 2014 Mar 4;22(3):452-65. doi: 10.1016/j.str.2013.12.014. PMID:24607143 doi:http://dx.doi.org/10.1016/j.str.2013.12.014
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