The structural basis of RNA-catalyzed RNA polymerization
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Bartel_The structural basis.pdf
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Author(s)
Shechner, David M
Bartel, David
Shechner, David M.
Date Issued
August 2011
Journal
Nature Structural & Molecular Biology
Publisher
Elsevier B.V.
Citation
Shechner, David M, and David P Bartel. “The structural basis of RNA-catalyzed RNA polymerization.” Nature Structural & Molecular Biology 18, no. 9 (August 21, 2011): 1036-1042.
Version
Author's final manuscript
Abstract
Early life presumably required polymerase ribozymes capable of replicating RNA. Known polymerase ribozymes best approximating such replicases use as their catalytic engine an RNA-ligase ribozyme originally selected from random RNA sequences. Here we report 3.15-Å crystal structures of this ligase trapped in catalytically viable preligation states, with the 3′-hydroxyl nucleophile positioned for in-line attack on the 5′-triphosphate. Guided by metal- and solvent-mediated interactions, the 5′-triphosphate hooks into the major groove of the adjoining RNA duplex in an unanticipated conformation. Two phosphates and the nucleophile jointly coordinate an active-site metal ion. Atomic mutagenesis experiments demonstrate that active-site nucleobase and hydroxyl groups also participate directly in catalysis, collectively playing a role that in proteinaceous polymerases is performed by a second metal ion. Thus artificial ribozymes can use complex catalytic strategies that differ markedly from those of analogous biological enzymes.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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Creative Commons Attribution-Noncommercial-Share Alike 3.0
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DOI of Published Version
https://doi.org/10.1038/nsmb.2107
