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Resolution-exchanged structural modeling and simulations jointly unravel that subunit rolling underlies the mechanism of programmed ribosomal frameshifting.
- Source :
-
Bioinformatics . 3/15/2019, Vol. 35 Issue 6, p945-952. 8p. - Publication Year :
- 2019
-
Abstract
- Motivation Programmed ribosomal frameshifting (PRF) is widely used by viruses and bacteria to produce different proteins from a single mRNA template. How steric hindrance of a PRF-stimulatory mRNA structure transiently modifies the conformational dynamics of the ribosome, and thereby allows tRNA slippage, remains elusive. Results Here, we leverage linear response theories and resolution-exchanged simulations to construct a structural/dynamics model that connects and rationalizes existing structural, single-molecule and mutagenesis data by resolution-exchanged structural modelling and simulations. Our combined theoretical techniques provide a temporal and spatial description of PRF with unprecedented mechanistic details. We discover that ribosomal unfolding of the PRF-stimulating pseudoknot exerts resistant forces on the mRNA entrance of the ribosome, and thereby drives 30S subunit rolling. Such motion distorts tRNAs, leads to tRNA slippage, and in turn serves as a delicate control of cis-element's unwinding forces over PRF. Availability and implementation All the simulation scripts and computational implementations of our methods/analyses (including linear response theory) are included in the bioStructureM suite, provided through GitHub at https://github.com/Yuan-Yu/bioStructureM. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]
- Subjects :
- *RIBOSOMES
*TRANSFER RNA
*GENE expression
*GENETIC code
*X-ray diffraction
Subjects
Details
- Language :
- English
- ISSN :
- 13674803
- Volume :
- 35
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Bioinformatics
- Publication Type :
- Academic Journal
- Accession number :
- 135381837
- Full Text :
- https://doi.org/10.1093/bioinformatics/bty762