Cap-specific mRNA (nucleoside-2'-O-)-methyltransferase 1 Protein in complex with capped RNA fragment
Classification:
TRANSFERASE/RNA
Technique:
X-Ray Diffraction
Resolution:
2.7
R value free:
0.241
R value observed:
0.185
R value work:
0.182
Abstract of the PDB Structure's related Publication:
The 5' cap of human messenger RNA contains 2'-O-methylation of the first and often second transcribed nucleotide that is important for its processing, translation and stability. Human enzymes that methylate these nucleotides, termed CMTr1 and CMTr2, respectively, have recently been identified. However, the structures of these enzymes and their mechanisms of action remain unknown. In the present study, we solve the crystal structures of the active CMTr1 catalytic domain in complex with a methyl group donor and a capped oligoribonucleotide, thereby revealing the mechanism of specific recognition of capped RNA. This mechanism differs significantly from viral enzymes, thus providing a framework for their specific targeting. Based on the crystal structure of CMTr1, a comparative model of the CMTr2 catalytic domain is generated. This model, together with mutational analysis, leads to the identification of residues involved in RNA and methyl group donor binding.
hMTr1 protein transfers a methyl group from S-adenosylmethionine to the 2'-O-ribose of the first nucleotide of messenger RNA and small nuclear RNA. N(7) methylation of the guanosine cap is not required for hMTr1 activity. Cellular eukaryotic mRNAs are capped at their 5' ends with a 7-methlylguanosine nucleotide, that plays a pivotal role in conferring mRNA stability. 7-methylguanosine stimulates mRNA biogenesis, namely splicing, poly (A) addition, nucleoplasmatic transport, and increasing translational efficiency ( Werner et al. 2011 ).