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Assembly constraints drive co-evolution among ribosomal constituents
- Source :
- Nucleic Acids Research
- Publication Year :
- 2015
- Publisher :
- Oxford University Press, 2015.
-
Abstract
- Ribosome biogenesis, a central and essential cellular process, occurs through sequential association and mutual co-folding of protein–RNA constituents in a well-defined assembly pathway. Here, we construct a network of co-evolving nucleotide/amino acid residues within the ribosome and demonstrate that assembly constraints are strong predictors of co-evolutionary patterns. Predictors of co-evolution include a wide spectrum of structural reconstitution events, such as cooperativity phenomenon, protein-induced rRNA reconstitutions, molecular packing of different rRNA domains, protein–rRNA recognition, etc. A correlation between folding rate of small globular proteins and their topological features is known. We have introduced an analogous topological characteristic for co-evolutionary network of ribosome, which allows us to differentiate between rRNA regions subjected to rapid reconstitutions from those hindered by kinetic traps. Furthermore, co-evolutionary patterns provide a biological basis for deleterious mutation sites and further allow prediction of potential antibiotic targeting sites. Understanding assembly pathways of multicomponent macromolecules remains a key challenge in biophysics. Our study provides a ‘proof of concept’ that directly relates co-evolution to biophysical interactions during multicomponent assembly and suggests predictive power to identify candidates for critical functional interactions as well as for assembly-blocking antibiotic target sites.
- Subjects :
- Models, Molecular
Ribosomal Proteins
RNA Folding
Globular protein
Ribosome biogenesis
Cooperativity
Ribosome Subunits, Small, Bacterial
Computational biology
Biology
Ribosome
Evolution, Molecular
RNA, Ribosomal, 16S
Genetics
Escherichia coli
Point Mutation
Nucleotide
chemistry.chemical_classification
Escherichia coli Proteins
Computational Biology
Ribosomal RNA
Folding (chemistry)
Kinetics
chemistry
Thermodynamics
Deleterious mutation
Subjects
Details
- Language :
- English
- ISSN :
- 13624962 and 03051048
- Volume :
- 43
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Nucleic Acids Research
- Accession number :
- edsair.doi.dedup.....8177e9cc399f47d95c7542ae5d7eca5c