The Structural Basis of Ribozyme-Catalyzed RNA Assembly
Open accessAbstract
Life originated, according to the RNA World hypothesis, from self-replicating ribozymes that catalyzed ligation of RNA fragments. We have solved the 2.6 angstrom crystal structure of a ligase ribozyme that catalyzes regiospecific formation of a 5' to 3' phosphodiester bond between the 5'-triphosphate and the 3'-hydroxyl termini of two RNA fragments. Invariant residues form tertiary contacts that stabilize a flexible stem of the ribozyme at the ligation site, where an essential magnesium ion coordinates three phosphates. The structure of the active site permits us to suggest how transition-state stabilization and a general base may catalyze the ligation reaction required for prebiotic RNA assembly.
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The L1 structure shows a bound metal ion in the active site, coordinated by three nonbridging phosphate oxygens, one of which belongs to the newly formed phosphodiester linkage.
“The L1 structure (Fig. 6A) shows a bound metal ion in the active site, coordinated by three nonbridging phosphate oxygens, one of which belongs to the newly formed phosphodiester linkage.”
From Protocells and RNA Self-Replication (2018) · cites this paper as Robertson and Scott 2007
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 Robertson and Scott 2007
RNA polymerase enzymes solve the problems of metal ion catalysis by binding and precisely positioning the metal ion for catalysis.
“RNA polymerase enzymes solve these problems by binding and precisely positioning the metal ion for catalysis (Zhang et al. 1999;Cramer et al. 2001;Robertson and Scott 2007;Shechner et al. 2009).”
From Protocells and RNA Self-Replication (2018) · cites this paper as Robertson and Scott 2007
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Robertson, M. P., & Joyce, G. F. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a003608 · Cited by 556 · see citing works
Self-citationProtocells and RNA Self-Replication
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- Authors
- Robertson, M. P., & Scott, W. G.
- Affiliations
- University of California, Santa Cruz (US)
- Corresponding author
- Scott, William G.
- Venue
- Science
- Published
- 2007-03-16
- Volume
- 315
- Issue
- 5818
- Pages
- 1549-1553
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2080284797
- Cited by
- 111
- References
- 4
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 3 · 2023: 3 · 2022: 2 · 2021: 1 · 2020: 4 · 2019: 5 · 2018: 6 · 2017: 5 · 2016: 3 · 2015: 5 · 2014: 7 · 2013: 2 · 2012: 10
- FWCI
- 5.44
- Type
- journal article
- Language
- en
- Open access
- green
- escholarship.org
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM087721)
- 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
- ribozymes, RNA ligase, RNA ligation, RNA world, phosphodiester bond formation, crystal structure, magnesium coordination, active site, transition state stabilization, general base catalysis, RNA tertiary structure
- MeSH terms
- Binding Sites, Catalysis, Crystallization, Hydrogen Bonding, Models, Molecular, Molecular Conformation, Nucleic Acid Conformation, Oligoribonucleotides, Ribonucleotides, Templates, Genetic, RNA, Catalytic, Crystallography, X-Ray, Directed Molecular Evolution, Base Pairing, Catalytic Domain
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