Molecular crowding stabilizes folded RNA structure by the excluded volume effect
Open accessAbstract
Crowder molecules in solution alter the equilibrium between folded and unfolded states of biological macromolecules. It is therefore critical to account for the influence of these other molecules when describing the folding of RNA inside the cell. Small angle X-ray scattering experiments are reported on a 64 kDa bacterial group I ribozyme in the presence of polyethylene-glycol 1000 (PEG-1000), a molecular crowder with an average molecular weight of 1000 Da. In agreement with expected excluded volume effects, PEG favors more compact RNA structures. First, the transition from the unfolded to the folded (more compact) state occurs at lower MgCl(2) concentrations in PEG. Second, the radius of gyration of the unfolded RNA decreases from 76 to 64 A as the PEG concentration increases from 0 to 20% wt/vol. Changes to water and ion activities were measured experimentally, and theoretical models were used to evaluate the excluded volume. We conclude that the dominant influence of the PEG crowder on the folding process is the excluded volume effect.
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Crowding effects contribute to the folding stability of ribozymes and reduce the effect of otherwise deleterious mutations.
“since crowding effects contribute to the folding stability of ribozymes [144–148] and reduce the effect of otherwise deleterious mutations [149].”
From The RNA world as a model system to study the origin of life (2015) · cites this paper as [146]
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- Authors
- Kilburn, D., Roh, J. H., Guo, L., Briber, R. M., & Woodson, S. A.
- Affiliations
- National Institute of Standards and Technology (US)
- Corresponding author
- Briber, Robert M.
- Woodson, Sarah A.
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2010-06-03
- Volume
- 132
- Issue
- 25
- Pages
- 8690-8696
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- PMC
- PMC2906142
- OpenAlex
- W2069122773
- Cited by
- 211
- References
- 48
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 15 · 2023: 10 · 2022: 15 · 2021: 15 · 2020: 12 · 2019: 10 · 2018: 10 · 2017: 13 · 2016: 11 · 2015: 12 · 2014: 16 · 2013: 22 · 2012: 12
- FWCI
- 6.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of the American Chemical Society (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (GM60819, R01GM060819)
- National Center for Research Resources (P41RR008630, RR08630)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- macromolecular crowding, RNA folding, excluded volume, group I ribozyme, polyethylene glycol, radius of gyration, magnesium ions, small-angle X-ray scattering
- MeSH terms
- Dose-Response Relationship, Drug, Nucleic Acid Conformation, Polyethylene Glycols, Water, X-Ray Diffraction, Magnesium Chloride, RNA, Catalytic, Azoarcus, RNA Stability, Scattering, Small Angle
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