title: Assembly constraints drive co-evolution among ribosomal constituents.
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.
authors.affiliation: Department of Biophysics, Molecular Biology and Bioinformatics, University of Calcutta, Kolkata 700009, West Bengal, India Center of Excellence in Systems Biology and Biomedical Engineering (TEQIP Phase II), University of Calcutta, Kolkata 700009, West Bengal, India.
authors.forename: Saurav
authors.initials: S
authors.lastname: Mallik
authors.affiliation: Division of Evolutionary Genetics, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan Department of Genetics, The Graduate University for Advanced Studies (SOKENDAI), 1111 Yata, Mishima, Shizuoka 411-8540, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Akashi
authors.affiliation: Department of Biophysics, Molecular Biology and Bioinformatics, University of Calcutta, Kolkata 700009, West Bengal, India Center of Excellence in Systems Biology and Biomedical Engineering (TEQIP Phase II), University of Calcutta, Kolkata 700009, West Bengal, India skbmbg@caluniv.ac.in.
authors.forename: Sudip
authors.initials: S
authors.lastname: Kundu
mesh_terms: D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D019143:Evolution, Molecular; D007700:Kinetics; D008958:Models, Molecular; D017354:Point Mutation; D059370:RNA Folding; D012336:RNA, Ribosomal, 16S / Q000737:chemistry*; D012269:Ribosomal Proteins / Q000737:chemistry* / Q000378:metabolism; D054680:Ribosome Subunits, Small, Bacterial / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D029968:Escherichia coli Proteins; D012336:RNA, Ribosomal, 16S; D012269:Ribosomal Proteins