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Structure and mechanism of the methyltransferase ribozyme MTR1

Please always quote using this URN: urn:nbn:de:bvb:20-opus-272170
  • RNA-catalysed RNA methylation was recently shown to be part of the catalytic repertoire of ribozymes. The methyltransferase ribozyme MTR1 catalyses the site-specific synthesis of 1-methyladenosine (m\(^1\)A) in RNA, using O\(^6\)-methylguanine (m\(^6\)G) as methyl group donor. Here we report the crystal structure of MTR1 at a resolution of 2.8 Å, 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 m1A-containing RNA product andRNA-catalysed RNA methylation was recently shown to be part of the catalytic repertoire of ribozymes. The methyltransferase ribozyme MTR1 catalyses the site-specific synthesis of 1-methyladenosine (m\(^1\)A) in RNA, using O\(^6\)-methylguanine (m\(^6\)G) as methyl group donor. Here we report the crystal structure of MTR1 at a resolution of 2.8 Å, 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 m1A-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.show moreshow less
Metadaten
Author: Carolin P. M. Scheitl, Mateusz Mieczkowski, Hermann SchindelinORCiD, Claudia HöbartnerORCiD
URN:urn:nbn:de:bvb:20-opus-272170
Document Type:Preprint
Faculties:Fakultät für Biologie / Rudolf-Virchow-Zentrum
Fakultät für Chemie und Pharmazie / Institut für Organische Chemie
Language:English
Parent Title (English):Nature Chemical Biology
Year of Completion:2022
Edition:submitted version
Source:Nature Chemical Biology (2022) 18, 547-555. https://doi.org/10.1038/s41589-022-00976-x
DOI:https://doi.org/10.1038/s41589-022-00976-x
Sonstige beteiligte Institutionen:Center for Nanosystems Chemistry (CNC), University of Würzburg
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften
Tag:Crystal structure of MTR1; Methyltransferase Ribozyme MTR1; RNA; RNA-catalyzed RNA methylation; X-ray crystallography
Release Date:2022/05/19
EU-Project number / Contract (GA) number:682586
OpenAIRE:OpenAIRE
Licence (German):License LogoDeutsches Urheberrecht