Structural highlights
Publication Abstract from PubMed
RNA-catalyzed RNA methylation was recently shown to be part of the catalytic repertoire of ribozymes. The methyltransferase ribozyme MTR1 catalyzes the site-specific synthesis of 1-methyladenosine (m(1)A) in RNA, using O(6)-methylguanine (m(6)G) as a methyl group donor. Here, we report the crystal structure of MTR1 at a resolution of 2.8 A, which reveals a guanine-binding site reminiscent of natural guanine riboswitches. The structure represents the postcatalytic state of a split ribozyme in complex with the m(1)A-containing RNA product and the demethylated cofactor guanine. The structural data suggest the mechanistic involvement of a protonated cytidine in the methyl transfer reaction. A synergistic effect of two 2'-O-methylated ribose residues in the active site results in accelerated methyl group transfer. Supported by these results, it seems plausible that modified nucleotides may have enhanced early RNA catalysis and that metabolite-binding riboswitches may resemble inactivated ribozymes that have lost their catalytic activity during evolution.
Structure and mechanism of the methyltransferase ribozyme MTR1.,Scheitl CPM, Mieczkowski M, Schindelin H, Hobartner C Nat Chem Biol. 2022 May;18(5):547-555. doi: 10.1038/s41589-022-00976-x. Epub 2022, Mar 17. PMID:35301481[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Scheitl CPM, Mieczkowski M, Schindelin H, Höbartner C. Structure and mechanism of the methyltransferase ribozyme MTR1. Nat Chem Biol. 2022 May;18(5):547-555. PMID:35301481 doi:10.1038/s41589-022-00976-x