Crystal Structure of the Catalytic Core of an RNA-Polymerase Ribozyme
Open accessAbstract
Primordial organisms of the putative RNA world would have required polymerase ribozymes able to replicate RNA. Known ribozymes with polymerase activity best approximating that needed for RNA replication contain at their catalytic core the class I RNA ligase, an artificial ribozyme with a catalytic rate among the fastest of known ribozymes. Here we present the 3.0 angstrom crystal structure of this ligase. The architecture resembles a tripod, its three legs converging near the ligation junction. Interacting with this tripod scaffold through a series of 10 minor-groove interactions (including two A-minor triads) is the unpaired segment that contributes to and organizes the active site. A cytosine nucleobase and two backbone phosphates abut the ligation junction; their location suggests a model for catalysis resembling that of proteinaceous polymerases.
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Both the L1 and class I ligases are dependent on Mg2+ ions for their activity.
“Both ligases are dependent on Mg 2+ ions for their activity.”
From Protocells and RNA Self-Replication (2018) · cites this paper as Shechner et al. 2009
The passages supplied from the paper’s Abstract report that class I ligase activity varies with Mg2+ concentration and propose a magnesium ion that is critical for catalysis. They also mention a catalytic metal-ion site in the L1 ligase, but do not specify that its ion is Mg2+ or establish that L1 activity depends on Mg2+. The claim about both ligases therefore goes beyond what our copy supports. (LLM, conf=0.82)
Experimental — accuracy not yet measuredIn the class I structure, no catalytic metal ion is seen in the vicinity of the active site, although there is what appears to be an empty metal-binding site formed by two nonbridging phosphate oxygens positioned directly opposite the ligation junction.
“In the class I structure (Fig. 6B), no catalytic metal ion is seen in the vicinity of the active site, although there is what appears to be an empty metalbinding site formed by two nonbridging phosphate oxygens, positioned directly opposite the ligation junction”
From Protocells and RNA Self-Replication (2018) · cites this paper as Shechner et al. 2009
The crystal structure of the Class I RNA ligase suggests that this linker sequence is positioned to interact with the downstream RNA template and could strengthen the ribozyme's sequence-general contacts with the upstream duplex, enhancing primer/template binding.
“Examination of the crystal structure of the Class I RNA ligase29,30, from which the catalytic core of the ribozyme polymerase is derived, suggests this sequence is well-positioned to interact with the downstream RNA template (Fig. 3a), and could augment the sequence-general contacts the ribozyme makes with the upstream duplex16,29,31 to enhance primer/template binding.”
From In-ice evolution of RNA polymerase ribozyme activity (2013) · cites this paper as [29]
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- Authors
- Shechner, D. M., Grant, R. A., Bagby, S. C., Koldobskaya, Y., Piccirilli, J. A., & Bartel, D. P.
- Affiliations
- Howard Hughes Medical Institute (US)
- Massachusetts Institute of Technology (US)
- Corresponding author
- Bartel, David P.
- Venue
- Science
- Published
- 2009-11-27
- Volume
- 326
- Issue
- 5957
- Pages
- 1271-1275
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3978776
- OpenAlex
- W2017272474
- Cited by
- 136
- References
- 24
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 8 · 2023: 9 · 2022: 5 · 2021: 11 · 2020: 5 · 2019: 4 · 2018: 6 · 2017: 4 · 2016: 3 · 2015: 6 · 2014: 15 · 2013: 5 · 2012: 7
- FWCI
- 5.36
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of General Medical Sciences (GM61835, R01GM061835, R37GM061835)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Physical Sciences › Physics and Astronomy › Astronomy and Astrophysics › Origins and Evolution of Life
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- catalytic core, RNA replication, RNA world, crystal structure, active site, ribozyme catalysis
- MeSH terms
- Base Sequence, Catalysis, Crystallization, Hydrogen Bonding, Hydrogen-Ion Concentration, Magnesium, Models, Molecular, Molecular Sequence Data, Nucleic Acid Conformation, Polynucleotide Ligases, Ribonucleotides, DNA-Directed RNA Polymerases, RNA, Catalytic, Crystallography, X-Ray, Base Pairing, Catalytic Domain
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