mRNA cap recognition: Dominant role of enhanced stacking interactions between methylated bases and protein aromatic side chains
AUTOR(ES)
Hu, Guanghui
FONTE
The National Academy of Sciences
RESUMO
We have determined, by high resolution x-ray analysis, 10 structures comprising the mRNA cap-specific methyltransferase VP39 or specific mutants thereof in the presence of methylated nucleobase analogs (N1-methyladenine, N3-methyladenine, N1-methylcytosine, N3-methylcytosine) and their unmethylated counterparts, or nucleoside N7-methylguanosine. Together with solution affinity studies and previous crystallographic data for N7-methylguanosine and its phosphorylated derivatives, these data demonstrate that only methylated, positively charged bases are bound, indicating that their enhanced stacking with two aromatic side chains of VP39 (Tyr 22 and Phe 180) plays a dominant role in cap recognition. Four key features characterize this stacking interaction: (i) near perfect parallel alignment between the sandwiched methylated bases and aromatic side chains, (ii) substantial areas of overlap in the two-stacked rings, (iii) a 3.4-Å interplanar spacing within the overlapping region, and (iv) positive charge in the heterocyclic nucleobase.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=22034Documentos Relacionados
- Ribosome-messenger recognition: mRNA target sites for ribosomal protein S1.
- Multiple methylated cap sequences in adenovirus type 2 early mRNA.
- The Role of Nuclear Cap Binding Protein Cbc1p of Yeast in mRNA Termination and Degradation
- Metal ion-mediated specific interactions between nucleic acid bases of polynucleotides and amino acid side chains of polypeptides.
- On the base-stacking in the 5'-terminal cap structure of mRNA: a fluorescence study.